Midterm 1 Notes
Midterm 1 Notes Bio Sci E109
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Bio Sci E109
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Lecture 1 Saturday September 26 Z 1S 713 PM Chapter 1 Cellular Physiology Volume and Composition of Body Fluids Distribution of Water in the Body Fluid Compartments Total body water total amount of uid or water 39 Accounts for 50 to 70 of body weight Total body water correlates inversely with body fat 39 Females have a lower amount of total body water due to the presence of adipose tissue which males do not have TOTAL BODY WATER l xtracnllular lluxd I I I I Interstitial tluod lPlasma Intracellular lluid I f Cell membrane Capillary wall Compartments of total body water 1 Intracellular Fluid ICF III Contained within the cell and is 23 of total body water 2 Extracellular Fluid ECF III Outside of the cell and is 13 of total body water Cl Compartments of ECF 1 Plasma uid circulation in the blood vessels and the smaller of the two compartments 2 Interstitial uid bathes the cells and larger of the two 0 A ultrafiltrate of plasma Formed by the ltration process that occurs in the capillary wall 9 Plasma and interstitial uid are separated by capillary walls Capillary walls are impermeable to large molecules therefore the interstitial uid does not contain molecules such as proteins ICF and ECF are separated by cell membranes Composition of Body Fluids Compartments Composition is not uniform Units of Measuring Solute Concentrations Amounts of solute expressed in moles equivalents or osmoles Concentrations of solute expressed in moles per liter molL equivalent per liter EqL or osmoles per liter OsmL III Usually expressed in milli Mole 6 X 1023 molecules of a substance Millimole l 1000 or 10A3 moles Equivalent the amount of charged ionized solute and is the number of moles of the solute multiplied by its valence Osmole number of particles into which a solutes dissociates into solution Osmolarity the concentration of particles in solution expressed as osmoles per liter El Solute does not dissociate into solution then osmolarity is equal to molarity III Solute does dissociate into more than one particle in solution then osmolarity equals molarity time number of particles in solution pH logarithmic term used to express concentration of H hydrogen III pH log10H means that pH decreases as concentration of H increases and vice versa Electroneutrality of Body Fluid Compartments Reading Notes Page 1 39 Principle of macroscopic electroneutrality each compartment must have the same concentration in mEqL of positive charges cations and negative charges anions III Separation of charges is not enough to measurably change bulk concentrations Composition of Intracellular Fluid and Extracellular Fluid 39 ECF Composition III Major cations Na El Balancing cations Cl and HCO3 IZI High concentrations of Ca2 III More basic high pH 39 ICF Composition III Major cations K and Mg2 El Balancing cations proteins and organic phosphates III Low concentration of Ca2 El More acidic low pH 39 Total solute concentration osmolarity is the same in ICF and ECF due to the free owing water across the cell membranes Creation of Concentration Differences across Cell Membranes 39 Difference in solute concentration across cell membranes are created and maintained by energy consuming transport mechanisms in the cell membranes III NaK ATPase pump Transports Na from ICF to ECF and K from ECF to ICF at the same time 9 ATP is required 9 Creates large gradients for Na and K that exist across cell membranes El Ca2 ATPase pump 9 The intracellular CA2 concentration is maintained at a level much lower than the extracellular Ca2 concentration 9 ATP is required III Transmembrane Na concentration gradient as energy source Establishes concentration differences in cell membrane 0 ATP not utilized El Cell membranes are not freely permeable to substances but are selective Concentration Differences between Plasma and Interstitial Fluids 39 Plasma compartment contains proteins that are negatively charged and interstitial uids does not 39 GibbsDonnan equilbrium proteins cause redistribution of small permeant cations and anions across capillary wall 39 GibbsDonnan ratio gives the plasma concentration relative to the interstitial uid concentration for anions and interstitial uid concentration to plasma for cations Characteristics of Cell Membranes Composed primarily of lipids and proteins Lipids consist of phospholipids cholesterol and glycolipids Lipid function gt High permeability of cell membranes to lipidsoluble substances ie carbon dioxide oxygen fatty acid and steroids It39s also responsible for gt Low permeability of cell membranes of watersoluble substances ie ions glucose and amino acids Proteins consist of transporters enzymes hormone receptors cell surface antigens and ion and water channels Phospholipid Component of Cell Membranes Consist of phosphorylated glycerol backbone and two fatty acid tails 39 Glycerol backbone also known as quotheadquot is hydrophilic likes water 39 Fatty acid tails are hydrophobic hates water Amphipathic having both hydrophilic and hydrophobic properties Monolayer is formed in A in which glycerol backbone dissolves in water phase and fatty acid tails dissolve in oil phase Water A K Lipid bilayer B shows orientation of fatty acid tails face other and the I 2 If V f N I I on v39 J L 39 ltf glycerol heads pomt away from each other dissolvmg aqueous solutions of the ICF and ECF Reading Notes Page 2 Lipid bilayer B shows orientation of fatty acid tails face other and the OH O glycerol heads point away from each other dissolving aqueous solutions of the 39 ICF and ECF o o o 0 Waler Protein Component of Cell Membranes alumna quotLIV Paulina mm 11 mum Iquot mlz39m pmlnn a quotw t mam lluul nun Can be integral or peripheral in the cell membranes 39 Integral membrane proteins embedded in and anchored to the cell membrane by hydrophobic interactions III Can be removed by disrupting the attachments to the lipid bilayer III Types 9 Transmembrane proteins span the entire lipid bilayer one or more times in contact with both ICF and ECF 0 Ex ligandbinding receptors ions channels and etc 9 Embedded in the membrane but does not span it 39 Peripheral membrane proteins not embedded into the membrane and are not covalently bound to cell membrane components El Loosely attached by electrostatic interactions III Can be removed by disrupting ionic or hydrogen bonds 9 Ex ankyrin anchors the cytoskeleton of red blood cells to an integral membrane transport protein Reading Notes Page 3 Lecture 2 Sunday September 27 21115 1 217 PM Chapter 1 Cellular Physiology Transport Across Cell Membranes There are multiple ways to transport substance across cell membranes 1 Downhill occurs by diffusion either simple or facilitated and requires no input metabolic energy a Simple not carrier mediated 2 Uphill occurs by active transport may be primary or secondary a Primary and secondary are distinguished by energy source i Primary requires direct input ii Secondary requires indirect input Carriermediated transport facilitated diffusion primary and secondary active transport all in involve integral membrane proteins gt Three features of cellmediated transport 1 Saturation carrier proteins have a limited number of binding sites for the solute i Transport maximum Tm point at which saturation is achieved and all binding sites are occupied Tm 5 Relationship between the rate A minermeniazm of carriermediated transport E quotSITEWm fa a y and solute concentration 3 FleaH 5 Equot HFquot Low solute concentrations E l Elmme IIquot yquot mmm increase transport rates and I HIP III39 Equot concentration increases II High solute concentration 39 transport rate levels off likllti ill39 l aliull 2 Stereospeci city binding sites for solute on the transport proteins are stereospecific 3 Competition binding sites for transported solutes may recognize bind and even transport chemically related solutes Simple Diffusion Diffusion of Nonelectrolytes 39 Simple diffusion occurs as a result of the random thermal motion of molecules Emma A is initially twice that of B however 73 39 solute molecules are in constant 1 motion therefore equal probability that molecule will cross membrane r Net d1ffus10n reater movement of E3 Q Q 3 g 1 molecules from A to R then R to A Reading Notes Page 4 LLLHL LLLULUUULU VV LLL U1 UUU LLLULLLUL LAU Net diffusion greater movement of molecules from A to B then B to A m until solute concentrations are equal t for both Flux Flow J net diffusion of solute and depends on size of concentration gradient partition coef cient diffusion coef cient thickness of membrane and surface area available for diffusion Concentration Gradient Ca Cb III Driving force for net diffusion the larger the difference between A and B the greater the force III Equal concentration means no driving force Partition Coef cient K III Describes the solubility of a solute in oil relative to its solubility in water III The greater the relative solubility the higher the partition coef cient and the more easily the solute can dissolve in the cell membrane39s lipid bilayer III Nonpolar solutes tend to have high values of partition coef cient Polar solutes tend to have low values of partition coef cient Measured by adding solute to mixture of oil and water and then measuring concentration in oil phase relative to water phase K concentration in oil concentration in water Diffusion Coef cient D III Depends on size of the molecule and the viscosity of the medium III Correlates inversely with the molecular radius of the solute and the viscosity of the medium III Small solutes have the largest diffusion coef cients and diffuse readily III Large solutes have the smallest diffusion coef cients and do not diffuse readily r Diliueiun E f ElE i i Eiil393iuaun5 constant D Z 52 1 T liberal EEC Mm r Mlecular 1m ins 111 Ei ii f the medium 1H L I ll Thickness of the Membrane AX III The thicker the cell the greater the distance the solute must diffuse and the lower the rate of diffusion Surface Area A III The greater the surface area of the membrane available the higher the rate of diffusion El Permeability the partition coef cient the diffusion coef cient and the membrane Reading Notes Page 5 thickness 1 ED p a H H El Rate of net diffusion J Farm EE 1 Huii rate of diffusiui irmmf aml CF 2 Permeability cruiser Surface area for iiiiu iun Emil 23 Ei i 39iif li il in Solution a liitiitii C l lt l lli li li 3911 S luiim E mnmnm Diffusion of Electrolytes 39 There are two consequences of the presence of charge on the solute such as an ion or an electrolyte 1 If there potential difference across the membrane then the potential difference will alter the net rate of diffusion of a charged solute 2 Diffusion potential when a charged solute diffuses down a concentration gradient that diffusion can itself generate a potential difference across a membrane Facilitated Diffusion Occurs down an electrochemical potential gradient thus it requires no input of metabolic energy Uses membrane carrier and exhibits all the characteristics of carriermediated transport saturation stereospecificity and competition Proceeds faster at low solute concentration because of the function of the carrier 39 Dglucose facilitated diffusion into skeletal muscle and adipose cells by the GLUT4 transporter Primary Active Transport Solute is moved from an area of low concentration to high concentration therefore ATP must be provided ATP is hydrolyzed to ADP and Pi releasing energy from terminal phosphate which is transferred to the transport protein thus initiating phosphorylation and dephosphorylation Primary active transport is when ATP energy source is directly coupled to the transport process 39 Ex Na K ATPase Ca2 ATPase and H K ATPase NaK ATPase Pump 39 Present in the membranes of all cells 39 Pumps Na from ICF to ECF and K from ECF to ICF 39 Every 3 Na pumped out of the cell two K are pumped into the cell B More positive charge is pumped out than in the cell III Electrogenic creates a charge separation and a potential difference 39 Responsible for maintaining concentration gradients for both Na and K across cell Reading Notes Page 6 membranes 39 Consists of two units III 0t subunit contains ATPase activity and the binding sites for the transported ions III 3 subunit 39 Major transformational states 1 E1 state the binding sites for Na and K face the ICF and has a high affinity for Na 2 E2 state the binding sites for Na and K face ECF and has a high affinity for K III Powered by ATP hydrolysis 39 Transport cycle switching between El and E2 states ll Era umair f Ji j iE mceiular uid In Ir39amllmar ui Ematimcnallmar rlluiij Enzyme in El state is bound to ATP and is hydrolyzed and becomes ElP and changes conformation to E2P Now in the E2 state the inorganic phosphate is released when 3 Na ions are released from enzyme binding ATP and enduring another conformational change to El state 2 K ions are released and another cycle begins 39 Cardiac glycosides class of drugs that inhibits Na K ATPase III Treatment causes changes in intracellular ionic concentration Na concentration increase K concentration decreases III Inhibit by binding to E2P near the K binding site preventing conversion back to El Ca2 ATPase Pump 39 Cell plasma membranes contain Ca2 ATPase PMCA 39 PMCA function is to extrude Ca2 from the cell against an electrochemical gradient III One Ca2 is extruded for each ATP hydrolyzed III Maintains low intracellular Ca2 concentration 39 Sarcoplasmic reticulum and endoplasmic reticulum SERCA contain variants of Ca2 ATPase that pump two Ca2 ions from ICF into the either reticulum 39 They have El and E2 states as well III PMCA El state binds Ca2 on ICF side and conformational change occurs to E2 state and the Ca2 is released to ECF III SERCA El state binds Ca2 on ICF side and the E2 state releases Ca2 to lumen of Reading Notes Page 7 either reticulum HK ATPase Pump 39 Found in parietal cells of the gastric mucosa and in the Otintercalated cells of the renal collecting duct 39 Pumps H from ICF of parietal cells to lumen of stomach 39 Omeprazole inhibitor used therapeutically to reduce the secretion of H in ulcer disease Secondary Active Transport Transport of two or more solutes is coupled Metabolic energy is supplied indirectly when for example Na concentration moves downhill providing energy for uphill movement of other solutes Inhibition diminishes the transportation of Na from ICF to ECF causing increase in Na concentration and decrease the size of the transmembrane Na gradient Two types 1 Cotransport symport uphill solute moves in the same direction as Na 2 Countertransport antiport or exchange uphill solute move in the opposite direction of Na Cotransport 39 Na and other solutes both move into the cell 39 Involved in absorbing epithelia of the small intestine and the renal tubule III Naglucose cotransport SGLT and Naamino acid cotransport 9 Luminal membranes of the epithelial cells of both small intestine and renal proximal tubule Lumen Intestinal epitholnal cell Blood E 79 3m Cotransporter has two recognition sites Na ATP Na and glucose When both present in scam139 2 lumen of the small intestine they bind to G39UCOSO G39UCOSQ transporter The cotransporter then rotates and releases both Na and glucose to the interior cell Luminal or Basolateral apical membrane membrane III Na K2Cl cotransport Luminal membrane of the epithelial cells of the thick ascending limb Countertransport 39 Na moves into the cell on the carrier and the solutes are countertransported or exchanged for Na move out of the cell Exchange protein has recognition sites for both Ca2 and Na Protein binds to Ca2 on the intracellular side and Na on extracellular side M u SGHE ca Ill Reading Notes Page 8 MUSEEE CiElll v A Ca2 and Na Protein binds to Ca2 on the intracellular side and Na on extracellular side The protein than rotates and delivers Ca2 to exterior and Na to interior of the cell 29 39 39 3 Na ions enter cell for each Ca2 ion extruded from cell making Ca2 Na exchanger electrogenic Reading Notes Page 9 Lecture 3 Wednesday September 330 2 15 512 PM Chapter 1 Cellular Physiology O O Osmosis Flow of water across a semipermeable membrane because of the differences in solute concentration Osmotic pressure established because of the concentration differences of impermeant solutes which cause wat to ow by osmosis Occurs because of a pressure difference 39 Diffusion occurs because of concentration difference of water Osmolarity 39 Concentration of osmotically active particles expressed as osmoles per liter 39 To calculate you need to know the concentration of the solute and whether it dissociates in solution III quotgquot gives number of particles in solution and takes into account whether is complete or only partial dissociation snmlal ly g L wlirw Isn39nnrialm39i lty Ji39nintuiiIin lt imn m i ia li39lliiif39L391i E il i39lll irl39l l g Hunnu mr of mr imzlujs nor quotmill in solution Elmn jml E Emmi11reaf rm 1 n39nrn l jl 39 Isosmotic same calculated osmolarity 39 Hyperosmotic solution with the highest osmolarities out of two different calculated osmolarities 39 Hyposmotic solution with the lowest osmolarities out of two different calculated osmolarities Osmolality 39 The concentration of osmotically active particles expressed as osmoles per kg of water III 1 kg of water is approximately equivalent to lL of water Osmotic Pressure Eat39sl lmarr rjwltjnhj V membrane 1 r J ii 7 v on v Q 3 a o a a 395 V 393 g r 7 G a 0 i E 1 2 A m 5 1 3 EH g 5 G L Equot Tinnah 393 3 U 393 l3 a 0 I f a n II r 7 r r r r r r 7 r r r r r r 7 r r r r r r 7 r r i 2 Pia unlazppehug 1 2 pressure in 541255 water th E Reading Notes Page 10 39 A Membrane is permeable to water but impermeable to solute Initially solute is only in solution 1 due to osmotic pressure due to the interaction with pores cause reduction in hydrostatic pressure in solution 1 which results in pressure difference causing water to ow from solution 2 to l 39 B the ow from solution 2 to l is preventer by applying pressure to a piston Osmotic pressure of solution 1 depends on the concentration of osmotically active particles and whether the solute remains in solution 1 39 Van39t Hoff equation calculate osmotic pressure I g L H Eli E 1 WWW 1n Bimini parri lun u aim or mm Hg as HIIEI EI IW If Stadiums lurr midt 13a millilitqu Usnlnflmll if 39lli iilmffl l llE iillrtf l nIirInm lf39l n m ltilrrtijunl HJEV IE lll ii39lllll varies i l l in In H t li 39IESE l l IHHIIHE I u lill fll il v It I lli lfli hquot titmleruniW Elli 39 Re ection coef cient 039 dimensionless number ranging between 0 and 1 that describes the ease with which a solute crosses a membrane III Conditions III 039 1 Membrane is impermeable to solute and solute retained in original solution Ex serum albumin intracellular proteins III 039 0 Membrane is freely permeable to the solute and solute will diffuse across the membrane down its concentration until solutions are equal Ex Urea III 039 a value between 0 and 1 Most solutes are neither impermeant nor freely permeant across membrane 1 T DEMEE J39I I BI39I EI ll E U Mnmtaranna 7 g V 0 ca 3 Gm 3 o r C 13 l C C1 3 Cquot 1 C if D V 39 Cl 3 a 3 i D 4 G C 3 1 39339 Clquot quot39139quot A E f A Diffusion Potentials and Equilibrium Potentials Ion Channels 0 Integral membranespanning proteins that when open permit the passage of certain ions 39 Selective allow ions with specific characteristics to move through them III Based on size of channel and charges lining it 39 Gates control ion channels by determining whether the channel is opened or closed based on the position of the gate III When channel is open ions pass via passive diffusiondown electrochemical gradient III When channel is closed ions cannot ow through III Controlled by 3 sensors Reading Notes Page 11 l Voltagegated channels controlled by changes in membrane potential i Ex activation gate on the nerve Na channel is opened by depolarization of the nerve cell membrane Inactivation gate is closed by depolarization and reacts slower than activation gate 2 Second messengergated channels controlled by changes in levels of intracellular signaling molecules such as cyclicAMP 3 Ligandgated channels controlled by hormones and neurotransmitters sensors located on the extracellular side of the ion channel 39 Conductance depends on the probability of the channel being open III The higher the probability that it is open the higher the conductance Diffusion Potentials O The potential difference generated across a membrane when a charged solute diffuses down its concentration gradient 39 Cause by diffusion of ions 39 Generated only if the membrane is permeable to that ion 0 Magnitude measured in millivolts mV depends on the size of the concentration gradient the driving force 39 Sign depends on the charge of the diffusion ion 0 Created by movement Equilibrium Potentials O The diffusion potential that exactly balances or opposes the tendency for diffusion down the concentration difference 0 Concentration difference for an ion across a membrane and the membrane is permeable to that ion potential difference is created 0 Electrochemical equilibrium the chemical and electrical driving forces acting on an ion are equal and opposite and no further net diffusion occurs Example of Na Equilibrium Potential FEIMHEHHMR XWE I 1 Na 3 Na pl nut My 2 LL Na El GI Equot i 1 El 1 2 1 E 39 Theoretical membrane that is permeable to Na separates two solutions Solution 1 has a higher concentration of NaCl and Na diffuses down concentration gradient from 1 to 2 Na diffusion potential develops due to the movement of positive charge to 2 and eventually prevents net diffusion of Na Na equilibrium potential is the potential difference that exactly balances the tendency of Na to diffuse down its concentration gradient Example of Cl Equilibrium Potential Reading Notes Page 12 4 Clquot ent 01 1 negatlve Reading Notes Page 13 Lecture 4 Thursday ct ber 1 Z 15 1125 AM IChapter 1 Cellular Physiology Nernst Equation 0 Used to calculate the equilibrium potential for an ion at a given concentration difference across a membrane 0 Equilibrium potential is calculated for one ion at a time lll l W III1 l i 3 l Em where l1 2 bllnililrrlum intertidal mm fur a given inquot E lijT 7 7 z Cunaram ll ENE at Met Eharge on the in 1 113 HE 33 M l 1531 Elf Ill 2 I39EIIMEEIWUJHT muc itm m will E IIEI39I Imlle 1 2 EMM Ellular f l li El ll T fi l I TE 34 WHENle O Converts concentration difference for an ion into a voltage 0 By convention membrane potential is expressed as intracellular potential relative to extracellular potential Driving Force 0 The difference between the actual measured membrane potential Em and ion39s calculated equilibrium potential EX 39 Uncharged solutes the concentration difference of the solute across the cell membrane 39 Charged solutes both concentration difference and the electrical potential difference across the cell membrane 0 The driving force on a given ion X is calculated as NEE rimming tum h39mt 2 E E15 where Driving fume 311an farce mm n39unl I nembrane pmen39tii II I I39WJ Enuililirimu p lE l l i fur E I39I Ell 39 When the driving force is negative Em is more negative than the ion39s equilibrium potential that the ion X Will enter the cell if it is a cation and leave if it is an anion and vice versa if the driving force is positive 39 If Em is equal to the ion39s equilibrium potential then the driving force on the ion is zero and the ion is at electrochemical equilibrium Ionic Current 0 IX or current ow occurs when there is movement of an ion across the cell membrane 0 Two conditions must be met for ions to move across channel Reading Notes Page 14 1 There is a driving force on the ion 2 Membrane has a conductance to that ion 391 T 7 i W in M innit chimera minimums innit mnduntannn Malina where nn n n anne 5 the maprnna if maintainer Em driving infra rm inn it Emit O Direction of ionic current determined by the direction of the driving force 0 Magnitude of ionic current determined by size of the driving force and the conductance 39 The greater the driving force the greater the current ow 39 The greater the conductance the greater the current ow 39 If driving force or conductance of an ion is zero there is not current ow Resting Membrane Potential The potential difference that exists across the membrane of excitable cells such as nerve and muscle Established by the diffusion potentials which results from the concentration differences for various ions across the cell membrane Each permeant ion attempts to drive the membrane potential towards its own equilibrium potential 70 to 80mV resting membrane potential of excitable cells Chord conductance equation evaluates the contribution that each ion makes to the membrane potential by weighing the equilibrium potential for each ion by its relative conductance E Elmquot L grit e Emit Tquot Er T quot ET Em Em ET I 1 JJJTL F WHERE Em r Martini am Iit39iiiliniiii Mt nit Hi tantalummin ELIE i liflrlil i mriiiirnnam if theirstartan g n nnntln anre if lil etc m Ea ermiiiilihmnn 15 it 1t El n 11m Goldman equation an alternative to the above considers the contribution of each ion by its relative permeability rather than by its conductance What role does the NaK AT Pase play in creating the resting membrane potential 1 Small direct electrogenic contribution of the NaK ATPase based on the stoichiometry of 3 Na ions pumped out for every 2 K pumped in the cell 2 Indirect contribution in maintaining the concentration gradient for K across the membrane which is responsible for K diffusion potential which drives the membrane potential toward K equilibrium potential Reading Notes Page 15 Lecture 5 Sunday ct ber 4 2 15 82 1 PM Chapter 1 Cellular Physiology Action Potentials Excitable cells such as nerve and muscle consist of a rapid depolarization upstroke followed by repolarization of the membrane potential Basic mechanism for transmission of information in the nervous system and all types of muscle Terminology O 0000 Depolarization process of making the membrane potential less negative on the interior of the cell It can all cause it to become more positive Hyperpolarization process of making the membrane potential more negative Inward current ow of positive charge into the cell depolarizing the membrane potential Outward current ow of positive charge out of the cell hyperpolarize the membrane potential Threshold potential membrane potential at which occurrence of the action potential is inevitable 39 Threshold is less negative than the rest of the membrane potential therefore an inward current is required to depolarize the membrane potential to threshold 39 Net inward current becomes larger than outward current and the resulting depolarization becomes selfsustaining therefore giving rise to action potential 39 Net inward current is smaller than outward current than membrane will not depolarized to threshold and action potential will not occur Overshoot portion of the action potential where the membrane potential is positive Undershoot also known as hyperpolarizing after potential portion of the action potential following repolarization where the membrane potential is actually more negative than it is at rest Refractory period period during which another normal action potential cannot be elicit in an excitable cell Characteristics of Action Potential 0 Stereotypical size and shape normal action potential looks identical for a given cell type depolarizes to the same potential and back to the same resting potential Propagation action potential at one site causes depolarization at adjacent sites bringing those adjacent sites to threshold 39 Nondecremental propagation of action potentials from one site to the next Allornone response action potential either occurs or not 39 If excitable cell is depolarized to threshold in normal manner the action potential occurs 39 If membrane is not depolarized to threshold action potential does not occur however if stimulus is applied during refractory period then action potential occurs without stereotypical size and shape or does not occur Ionic Basis of the Action Potential Reading Notes Page 16 Imam rI el r 211 Kill1m mm Farms 433 m Hm MIME f major nilEzul l Eff f i 5 i F i r r V Hi 39 Ii Ill g ll39l39lllllr uh I39 i HI HF u quot l l A E if i391 Fi If U quot I I all I l iii E H l1 i gulp 1e LE E if a sip a H IVIIZEII39TEEIEIJI39HIJP In in illL Elli m V l 39II I 53 En 3 33 m 39 35 3Liim1 quotFquot i quot a Jquot In nh k lial 35 llTL39iir quot E1 WMM Manual I I 1ZI 1 Tum lillrlll ieli illi39l39msli i ii potential 2 Upstroke of the action potential inward current causes depolarization of the nerve cell membrane to l Resting membrane potential membrane potential is 70mV at rest K conductance or permeability is high therefore allowing the diffusion of K ions out of the cell and down the concentration gradient This diffusion creates K diffusion potential which drives membrane potential towards the K equilibrium potential At rest Na conductance is low therefore resting membrane potential is far from Na equilibrium threshold occurs at 60mV i This causes rapid opening of activation gates of the Na channel and conductance increase becoming higher than K resulting in inward current Tetrodotoxin and lidocaine block the Na channels preventing occurrence of action potential i1 3 Repolarization of the action potential upstroke is terminated and the membrane potential repolarizes to the resting level This occurs because the inactivation gates of Na channels respond to depolarization by closing but i its slower than activation gates Therefore after the delay the inactivation gates close the Na channels terminating the upstroke ii Depolarization opens K channels increasing its conductance higher than Na which results in an outward K current and the membrane is repolarized Tetraethylammonium TEA blocks voltagegated K channels 111 than at rest and membrane potential is driven closer to K equilibrium potential When K returns to rest membrane potential depolarizes slightly back to resting potential and the 4 Hyperpolarizing afterpotential undershoot following repolarization the K conductance is higher i membrane is now ready to be stimulated to generate action potential The Nerve Na Channel 0 Voltagegated Na channel is an integral protein that is responsible for the upstroke of the action potential 39 Consist of a large 0 subunit and two 3 subunits 39 0t subunit has 4 domains which has 6 transmembrane Othelices which surround a pore that allow the ow of Na ions Reading Notes Page 17 39 Response to depolarization MiraJilin mini 1 At rest activation gate is closed therefore Na cannot ow through despite inactivation gate being open 2 During upstroke of the action potential depolarization to threshold causes activation gate to open therefore brie y allowing Na ions to ow through 3 At peak of action potential the inactivation has a delayed response and closes and repolarization begins until it reaches resting level therefore closing activation gate and opening inactivation gate Refractory Periods O Excitable cells are incapable of producing normal action potentials Absolute Refractory Period 39 Overlaps with almost the entire duration of the action potential during this time another action potential cannot be elicited 39 Provides closure of the inactivation gates of the Na channel in response to depolarization Relative Refractory Period 39 Begins at the end of the absolute refractory period and overlaps primarily with the priod of hyperpolarizing afterpotential and during this time an action potential can be elicited 39 Inward current is needed to bring the membrane to threshold for the next action potential because membrane potential is closer to the K equilibrium potential Accommodation 39 When the threshold potential may pass without an action potential having been fired occurs due to depolarization which closes inactivation gates on the Na channels III Ex hyperkalemia people with elevated serum K concentration Propagation of Action Potentials O Occurs by the spread of local currents from active regions to adjacent inactive regions Reading Notes Page 18 Mtggala mun 39 A initial segment of the nerve axon is depolarized to threshold and res an action potential The polarity is then reversed due to the inward Na current causing the cell interior to be positive The adjacent region remains negative 39 B at the active site positive charges inside the cell ow toward negative charges at the adjacent inactive sire causing the adjacent region to depolarize to threshold 39 C adjacent region of the axon res action potential Polarity of the membrane potential is reversed and the inside of the cell becomes positives while the active region is repolarized back to resting membrane potential and the cell is negative inside Changes in Conduction Velocity 39 Two mechanisms that increase velocity along a nerve 1 Increasing nerve diameter internal resistance Ri is inversely proportional to the cross sectional area therefore the larger the ber the lower the Ri Length constant is inversely proportional to the square root of Ri therefore when length constant is large when Ri is small The largest nerves have the longest length constant current spreads farthest 2 Myelination Myelin is a lipid insulator of nerve axons that increases Rm and decreases Cm a Increased Rm current ows along the path of least resistance of the axon interior rather than across the high resistance path of the axonal membrane b Decreased Cm produces a decrease in time constant therefore at breaks in myelin sheath the axonal membrane depolarizes faster in response to inward current 39 Nodes of Ranvier breaks in the myelin sheath causing there to be low Rm and current can ow across the membrane and action potentials can occur III Saltatory conduction action potentials quotjumpquot long distances from one node to the next Synaptic and Neuromuscular Transmission Synapse site where information is transmitted from one cell to another either electrically or via chemical transmitter Types of Synapses Electrical Synapses 39 Allow current to ow from one excitable cell to the next via low resistance pathways between the cells called gap junctions El Account for very fast conduction in cardiac muscle and some types of smooth muscle tissue Chemical Synapses Reading Notes Page 19 39 Gap between the presynaptic cell membrane and the postsynaptic cell membrane called the synaptic cleft 39 Information is transmitted across the synaptic cleft via neurotransmitters a substance that is release from the presynaptic terminal and binds to receptors on the postsynaptic terminal 39 Unidirectional from presynaptic to postsynaptic 39 Synaptic delay time required for the multiple steps in chemical neurotransmission to occur Neuromuscular Junction Example of a Chemical Synapse Motor Units 39 Motoneurons nerves the innervate muscle bers 39 Motor unit single motoneuron and muscle ber innervates it Sequence of Events at the Neuromuscular Junction 39 Neuromuscular junction synapse between a motoneuron and muscle ber H THEU ii HUSELE Fma lmp a innma tar minai HE EVEEl Ei EEI Hf Il mumr 1 mm WEE I39HJEI 39 J9 WE Hil 39lilflilii iii i ifl if EITEE39ETHFJ39TEZ ETITIIIliiilL E39 li i li i l LEIquot WEE WEHTI EWIJ Jl f i m ags iai39laa39lriala and Ira Ina ma immili39lal a AEE ti iIri tlillnEI iiiam I5 aim ma a39yrriapaa an aim J Ii Mi i IEIIFiIZJE ITEI TEES I39IZ IZEI ZIEDI iii m bl i and Ham 5 EI39TIEIE39il39i E F l Pia39 arid lEZ39 El DEERE m iiia mama arm tiara a WWI l i l l i a1 aria mainr anal plaia mnaaa amlmi mmmlaia in ganaraiam in limit adjEmmi FiTIIJEZIIZ39 IISELLEE Equot IELIEI TI E degraded m EWWE and ll11mm Wai 39 V IJITEIEI39 L CI iEi ia iaizan ham Iran iina iiraaymaaitia ianmmai an an iiamlmllma miraaamriai Agents That Alter Neuromuscular Function REFINE A a ti g Hummuaamar Tra amlasmn Eaamaiia Marian Hiram ma Hm39iamalar iiaifiiliimla imam Email Nauaiigmiim Halalit39haiiiiiiinri ilaalliza i ii h ralaa aa Tram pmayaanizia Tana hinalaadia pmaliiaiia rilf iEanairaiaaa mliaclmi aaii iarminraia riaailii lampEma ariiii fair maepima an aaraaaaa aiaa if EFF in mamimai adaaaa familiaaa riluiur and malaria paraiiiiraia impiraiimy unilaialea and milli MIhE iliiiihiim aititzlfiuliiaaiiaraaej FILill g and eerllliarlima airtiml Ui iiijiil an Initial and plantar Iiiluiiiia maintakie iii ulalinra iillli Depeiaa l aiurea iIIL39II1 praayanaptii ian39iiinail meay39iiapiia terminal sti ing Metalsingling hEhE aaaiyrlKril Ialii laalaraaa EPE and plain platanimal Types of Synaptic Arrangements 0 Onetoone synapses a single action potential in the presynaptic cell the motoneuron causes a single action potential in the postsynaptic cell the muscle ber 0 Onetomany synapses an action potential in the presynaptic cell the motoneuron causes a burst of Reading Notes Page 20 action potentials in the postsynaptic cells causes ampli cation of activity 0 Manytoone synapses action potential in the presynaptic cell is insuf cient to produce an action potential in the postsynaptic cell therefore many presynaptic cells converge on the postsynaptic cell and the inputs determine whether the postsynaptic cell will re an action potential Synaptic Input Excitatory and Inhibitory Postsynaptic Potentials O The manytoone synaptic arrangement is a common con guration in which many presynaptic cells converge on a single postsynaptic cell with inputs being either excitatory or inhibitory Excitatory Postsynaptic Potentials 39 EPSPs are synaptic inputs that depolarize the postsynaptic cell bringing the membrane potential closer to threshold and closer to ring an action potential 39 Produced by opening Na and K channels Inhibitory Postsynaptic Potentials 39 IPSPs are synaptic inputs that hyperpolarize the postsynaptic cell taking the membrane potential away from the threshold and farther from ring an action potential 39 Produced by opening Cl channels Integration of Synaptic Information 0 Presynaptic information that arrives at the synapse can be integrated in two ways Spatial Summation 39 Occurs when two or more presynaptic inputs arrive at a postsynaptic cell simultaneously 39 If they are both excitatory they combine to create a greater depolarization if one of them is excitatory they cancel each other out 39 Can occur when inputs are far apart as well Temporal Summation 39 Two presynaptic inputs arrive at the postsynaptic cell in rapid succession Other Phenomena That Alter Synaptic Activity 39 Facilitation augmentation and posttetanic potentiation repeated stimulus causes the response of the postsynaptic cell to be greater than expected by an increased release of neurotransmitters into the synapse by accumulation of Ca2 in presynaptic terminal 39 Longterm potential occurs in storage of memories and involves increased release of neurotransmitters from presynaptic terminals and increased sensitivity of postsynaptic membranes to the transmitter 39 Synaptic fatigue occur where repeated stimulus produces a smaller than expected response in the postsynaptic cell resulting from depletion of neurotransmitter stores from the presynaptic terminal Neurotransmitters 0 Transmission of information at chemical synapses involves the release of a neurotransmitter from a presynaptic cell diffusion across the synaptic cleft and binding of the neurotransmitter to speci c receptors on the postsynaptic membrane to produce a change in membrane potential Acetylcholine 39 Ach is the only neurotransmitter that is utilized at the neuromuscular junction 39 Released from all preganglionic and most postganglionic neurons in the parasympathetic nervous system and from all preganglionic neurons in the sympathetic nervous system 39 Released from presynaptic neurons of the adrenal medulla ll 7 a H Choline and acetyl CoA combine to form ACh Reading Notes Page 21 39 Released from presynaptic neurons of the adrenal medulla if Choline and acetyl CoA combine to form ACh Eh lm newi an wh1ch 1s catalyzed by choline acetyltransferase Ey hgg mammgm g Ach is released from presynaptic nerve terminal and diffuses into postsynaptic membrane where ngpi kg it binds and activates nicotinic ACh receptors AChE degrades ACh to choline and acetate i which terminates the action of ACh at the agrantHm WWWE39 postsynaptic membrane 12 of the choline is taken back into presynaptic terminal to be quotEmma Ema reutilized for synthesis Reading Notes Page 22 Lecture 6 Tuesday ct ber 6 2 15 622 PM Chapter 1 Cellular Physiology Skeletal Muscle Excitationcontraction coupling events that occur between the action potential in the muscle ber and contraction of the muscle ber Muscle Filaments 0 Each muscle ber behaves as a single unit multinucleate and contains myo brils 39 Myo brils are surrounded by sarcoplasmic reticulum and are invaginated by transverse tubules Think laments Thin MamEH11 ErmaSin arming tropomyosin mpnnim Tail Trmp mwsir Thick Filament 39 Comprised of III Myosin large molecular weight protein that has 6 polypeptide chains 1 pair of heavy chains and 2 pair of light chains III Heavy chains have a helical structure forming the tail III The four light chains form the globular head which have actinbinding site Thin Filaments 39 Composed of three proteins III Actin Globular protein called G actin Polymerized into two strands that twist into a helical structure to form lamentous action F actin Contains myosinbinding sites III Tropomyosin lamentous protein that runs along the groove of each twisted actin lament Function is to block the myosinbinding site when at rest III Troponin complex of three globular proteins troponin T troponin I and troponin C located along intervals of the tropomyosin lament Troponin T attaches troponin to tropomyosin Troponin I inhibits the interaction of action and myosin by covering the myosinbinding site Troponin C Ca2 binding protein plays role in initiation of contraction 0 Intracellular Ca2 increases Ca2 binds to troponin C producing functional change in troponin complex which moves tropomyosin out of the way permitting the binding of actin Arrangement of Thick and Thin Filaments in Sarcomeres Reading Notes Page 23 m1 Illaamend F 11mm Manama qu g g 5 mgff y u z x jf cL H Era I 2 2 14quot 3 r 7 L m w 71 39 39 knja n i Ej u t n j 7 it 1 r r 1 712 ztxzxigzvrgzyrgi zgmrxzx i3 EEK 1 i1 139 as i1 1 FG 7 a I2 1quot La arr K a E n bland ll Jami M 33mm 39 Sarcomere basic contractile unit that is delineated by the Z disks III Each contains a full A band in the center and 12 of 2 I bands on either side of the A band 39 A bands located in the center contain thick laments that appear dark under polarized light III Can be overlapping of thick and thin filaments resulting in sites for crossbridge formation 39 I bands located on either side of A bands appear light under polarized light III Contain thin filaments intermediate filamentous proteins and Z disks III No thick laments 39 Z disks darkly staining structure that runs down the middle of I bands 39 Bare zone located in center of each sarcomere and contains no thin filaments or thick filaments 39 M line bisects the bare zone and contains darkly staining proteins the link central portions of thick filaments together Cytoskeletal Proteins 39 Establish the structure of myofibrils ensuring the thick and thin filaments are aligned correctly and at proper distances from one another 39 Transverse CP link thick and thin filaments forming a scaffold for myofibrils and linking sarcomeres of adjacent myofibrils 39 Dystrophin an actin binding protein that anchors entire myofibril array to cell membrane 39 Longitudinal CP includes titin and nebulin proteins III Titin associated with thick filaments extends from M lines to Z disks Part of it passes through the thick filament and the rest is elastic which is anchored to Z disk The elastic portion changes as sarcomere length changes Helps center the thick filament in the sarcomere III Nebulin associated with thin filament single nebulin extends from one end of the thin filament to the other and serves as a quotmolecular rulerquot III a Actinin anchors the thin filament to Z disk Transverse Tubules and Sarcoplasmic Reticulum 39 Transverse T tubules extensive network of muscle cell membrane that invaginates deep into the muscle fiber III Carries depolarization from action potentials at the muscle cell surface to the interior of the fiber III Dthydropyridine receptor a voltage sensitive protein that is in the terminal cisternae of the sarcoplasmic reticulum with which T tubules make contact with 39 Sarcoplasmic reticulum internal tubular structure that stores and releases Ca2 for excitationcontraction coupling III Contains a Ca2 release channel called ryanodine receptor 39 Ca2 ATPase SERCA Ca2 accumulation in the sarcoplasmic reticulum III Pumps Ca2 from ICF of the muscle fiber into the interior of the sarcoplasmic reticulum keeping intracellular Ca2 low when the muscle fiber is at rest III Calsequestrin low affinity high capacity Ca2 binding protein Helps main low levels of Ca2 in the SR Reading Notes Page 24 ExcitationContraction Coupling in Skeletal Muscle O a mechanism that translates the muscle action potential into the production of tension 0 Temporal relationships are critical in that the action potential always precedes the rise in intracellular Ca2 concentration which always precedes contraction 0 Steps EEGI I ITI39IEIH IIE39I39 FMI2quotI391III H IHKEi El ETM HUBBLE Mllen mnlnl m mach manMm I e an mwmn m 139 runs a rareom 5 915 mkm wna n ii39il 39snulmr i m j T 1quot 39l lmsmi ar I139quot minim E as hmlrszpmij J 39I Iwgmn mu ar ulnas HelmquotJam Ilzijn 3111 magiu E Earning and mmraim w IiiBF l ifELI39E39UELL39EU Ezra Ir rutImamquot 0 Cross Bridge Cycling Position of Actln and Myosin Durlng Crossbrldge Cycllng Actm filament e r G Myosnn head Myosm tulamom O A D B 9 C 9 D e L A 1 Action potentials in muscle cell membrane are propagated to the T tubules 2 Depolarization of the T tubules causes conformational change in voltagesensitive dihydropyridine receptors Ca2 channels are opened 3 Increase in intracellular Ca2 concentration 4 Ca2 binds to troponin C on the thin filaments causing conformational change in the troponin complex 5 Conformational change causes tropomyosin to be moved out of the way so that crossbridge cycling can begin 6 Cross bridge cycling and the formation of bridges is associated with generation of force 7 Relaxation occurs when Ca2 is reaccumulated in the SR by Ca2 ATPase Events ATPADP Rugor No nucleohdes bound ATP binds to cleft on myosun head Conformational change so myosm AT P bound Decreased amnny of myosan tor actin Myosin released Cleft closes around ATP Contormatronal change M p ADP p39 Myosin head displaced toward G end ADP p bound 0 actin ATP hydrotyss Myosm head bonds new site on actin ADP bound Power stroke loroe ADP released Reading Notes Page 25 1 2 3 4 5 No ATP is bound to myosin which is tightly attached to actin in a quotrigorquot position The binding of the ATP to a cleft produces conformational change in myosin which decrease affinity of actin Cleft encloses the ATP molecules producing further conformational change which causes myosin to be displace toward positive end of actin and ATP is hydrolyzed Myosin binds to new site on actin constituting the force generating power stroke Each cross bridge cycle walks 10 nanometers along actin filament ADP is released and myosin returns to original position original position ADP released No nucleotides bound Rigor E Mechanism of Tetanus 0 Single action potential results in the release of a xed amount of Ca2 from the SR to produce a single twitch 39 Twitch is terminated when SR reaccumulates Ca2 39 How stimulus of the muscle can cause there to be insuffient time for reaccumulation of Ca2 this results in continuous binding of Ca2 to troponin C and a tetanus contraction occurs LengthTension Relationship 0 Refers to the effect of muscle fiber length on the amount of tension the fiber can develop 0 Isometric contraction muscle allowed to develop tension at a preset length called preload but it not allowed to shorten 39 Passive tension tension developed by simply stretching a muscle to different lengths 39 Total tension tension developed when a muscle is stimulated to contract at different preloads The sum of active tension and passive tension 39 Active tension determined by subtracting the passive tension from the total tensions represents the active force developed during crossbridge cycling 0 Unusual relationship between active tension and muscle length 0 Active tension developed is proportional to the number of crossbridge that cycle therefore active tension is maximal when there is a maximal overlap of thick and thin filaments and possible crossbridges 39 When muscle is stretched to longer lengths less crossbridges and active tension reduced and vice versa TE Si CH1 quot N Length at maximum 5 a cm5b dgre overlap N R Muscle length or preload Reading Notes Page 26 Lecture 7 Menday cteber 12 2 15 938 AM IChapter 1 Cellular Physiology Smooth Muscle Lacks striations therefore distinguishes it from skeletal and cardiac muscle 0 Striations are made of thin and thick laments in sarcomeres but in smooth muscle striations lack because the thin and thick laments are not organized in sarcomeres Founds in walls of hollow organs gastrointestinal tract bladder the uterus Functions 0 To produce motility and to maintain tension Types of Smooth Muscle O Classi ed as multiunit or unitary depending on whether they are electrically coupled or not 39 Unitary smooth muscle have gap junctions between cells which allow for fast spread of electrical activity throughout the organ followed by coordinated contraction 39 Multiunit smooth muscle has little or no coupling between cell 39 Combined smooth muscle only found in vascular smooth muscle Unitary Smooth Muscle 39 Present in gastrointestinal tract bladder uterus and ureter 39 Contract in coordinated fashion due to cells that are linked by gap junctions III Low resistance pathways for current ow which permits electrical coupling between cells 39 Slow waves spontaneous pacemaker activity also characterizes the unitary smooth muscle III Frequency of waves sets characteristic pattern of action potentials within an organ this then determines the frequency of contractions Multiunit Smooth Muscle 39 Present in the iris the ciliary muscles of the lens and the vas deferens 39 Each muscle ber behaves as a separate motor unit and there is little to no coupling between cells 39 Densely innervated by postganglionic bers of the parasympathetic and sympathetic nervous systems which regulate function ExcitationContraction Coupling in Smooth Muscle 0 There is troponin so the interaction of actin and myosin is controlled by the binding of Ca2 to another protein called calmodulin which regulates myosinlightchain kinase and regulates crossbridge cycling Mechanisms that Increase Intracellular Ca2 Concentration in Smooth Muscle HMSEEE EELL H HumaneEur 51 7 gt quot 7 a Ca agrant Reading Notes Page 27 iglLLiETEUE SELL HormoneDr FITIEELII39EIEIE39I Ermltar I quot i F5 Ea wattageWM A Ea channel uprna l dl Ea hannal A i Home Izir TiEli Elf I1 ii i i l f a mplasmilz reli llur m nah ILiglandigial Iad Gait Iihannra 39 Voltagegated Ca2 channels sarcolemmal Ca2 channels that open when the cell membrane potential depolarizes This allows action potentials in SM to cause voltage gated Ca2 channels to open allowing the ow of Ca2 into the cell down electrochemical gradient 39 Ligandgated Ca2 channels regulated by receptormediated events III Various hormones or neurotransmitters interact with speci c receptors in the sarcolemmal membrane which are couples Via GTPbinding protein to the Ca2 channels When the channel opens Ca2 ows into the cell 39 IP3gated Ca2 channels present in sarcoplasmic reticulum membrane rather than ECF III Hormones or neurotransmitters interact with speci c receptors on the sarcolemmal membrane which are coupled Via GTPbinding protein to phospholipase C Phospholipase C catalyzes hydrolysis of PIP2 to 1P3 and DAG III 1P3 diffuses into sarcoplasmic reticulum where Ca2 is released which channels owing from storage sites into ICF Reading Notes Page 28 Lecture 8 Monday Ct ber 12 2 15 93 AM Chapter 2 Autonomic Nervous System Somatic nervous system voluntary motor system under conscious control Consist of singular motoneuron and the skeletal muscle bers it innervates This is located in the central nervous system CNS which consist of the brain and spinal cord ACh is released from presynaptic terminals and activates receptors on motor end plates of skeletal muscle which causes an action potential This leads to contractions Autonomic nervous system involuntary system that controls and modulates the mctions primarily of visceral organs Consists of two neurons in each pathway preganglionic resides in CNS and release ACh and postganglionic travel through periphery and release either ACh or norepinephrine Organization and General Features of the Autonomic Nervous System Has two major divisions sympathetic and parasympathetic which complement each other in the regulation of the organ system 0 Also a third one enteric nervous system which located in the plexuses of the gastrointestinal tract EEHTHM HEFWCIUE Ev i39TE39ll39Elnl EFFEETGIH IEIFIEHHS Mutnuneumn Shelarial mum III a g E E g i 39 Pregang ani g Puatganglinnii smmmrhmi iii ACh 39 I Eir39nnnzh muEE EH glands i nil 39 vglanlzilisxF thaganglinni Pnatgang nnh Fa raaarmpalhcliiI A h ltMl I1 Pixl eg fln rrglitjm nk b I Mrenallmeduilia j qimgh wk EFmBF39hW39IB aw394 39 Mnrapinaphnna Emile n lf u m riliz lu ai Terminology Sympathetic and parasympathetic are anatomic terms that refer to preganglionic neurons in the CNS 39 Preganglionic neurons in the sympathetic division originate in the thoracolumbar spinal cord 39 Preganglionic neurons in the parasympathetic division originate in the brain stem and sacral spinal cord Adrenergic neurons that release norepinephrine and activate adrenoreceptors Cholinergic neurons release ACh to activate cholinoreceptors Neuroeffector Junctions of the Autonomic Nervous System Neuroeffector junctions are between postganglionic autonomic neurons and their target tissues which are analogous to the neuromuscular junctions of the somatic nervous system 39 Structural and inctional differences with neuromuscular junction 1 The neuromuscular junction has a discrete arrangement whereby the target tissue effector is innervated by a single motoneuron a In the autonomic nervous system the postganglionic neurons form diffuse branching networks which are lined by varicosities beads and are the site for neuron synthesis storage and release 2 Overlap in the branching networks from different postganglionic neurons 3 In autonomic nervous system postsynaptic receptors are widely distributed on the target tissues and there is not specializedregion Sympathetic Nervous System SVMPAYHETIC NERVOUS SYSTEM 3 huge 39rusm I mnnml grim Suptnor normal 1 umquotle 39 Hmlml I39mMu Twpnu mud n CIT 3 Main5 puI39d quotquot quotquot quotquot The inction is the mobilize the body for activity Irul until 39NJIMI 3M 39 Sympathetic nervous system is activated in response to ght or ight situations mum gar 39 Sympathetic chain one category of preganglionic neuron synapses on postganglionic neurons Hm 39 Prevertebral ganglia category of preganglionic neuron passes through the sympathetic chain without synapsing and continues on to synapse IF31039 US365 33910 SWEET glans rnr lLal hm Reading Notes Page 29 Picgauguuuiu llUulUll Pabbcb Llllngll L115 sympathetic chain without synapsing and continues on to synapse 39Zf39tillujl USUES 311C Unr cl xal lmn rev x r 12mm 3 rum 1 h a39nmll lull mllrw a Alluvial quotradium Ln unlnslnn I p r Inlrlrnr r 39 gt I v x l39lC39SHleWII plexus 393 i I r 39r v I quotv r I V r r rquot V I 39V I I I fiynrpallurlmz 393 quot tivrmmllmtz i l I clmln Imam quot Location of Autonomic Ganglia 39 Located near the spinal cord in either the paravertebral ganglia or in the prevertebral ganglia Mair nmlmllil 39 Superior cervical ganglion projects to the organs in the head and the celiac ganglion projects to the stomach and small intestine 39 Superior mesenteric ganglion projects to the small and large intestine and the inferior mesenteric ganglion projects to the bwer large intestine anus bladder and genitalia Adrenal medulla is a specialized sympathetic ganglion whose preganglionic neurons originate in the thoracic spinal cord and pass through sympathetic chain without synapsing and travel to the adrenal gland Length of Preganglionic and Postganglionic Axons 39 Preganglionic nerve axons are short because they are near the spinal cord and the postganglionic nerve axons are long Neurotransmitters and Types of Receptors 39 Preganglionic neurons are always cholinergic and they releases ACh which interact with nicotinic receptors of the postganglicnic neurons 39 Postganglionic neurons are adrenergic in all the tissue targets except in the thermoregulatory sweat glands where they are dlolinergic El The sympathetic adrenergic neurons have more than one receptor and the cholinergic neurons have muscarinic cholinoreceptors Adrenal Medulla 39 Specialized ganglion in the sympathetic division I The preganglionic neurons are located in the thoracic spinal cord and the axons travel in the greater splanchnic nerve to theadrenal medulla where they synapse on chromaf n cells This release ACH which activates the receptors and the chromaf n cells secrete catecholamines into the gereral circulation 39 The postganglionic neurons release only norepinephrine and the adrenal medulla secretes mainly epinephrine an a small amountof norepinephrine which is due to the presence of PNMT phenylethanilamine Nmethyltransferase III PNMT catalyzes the conversion of norepinephrine to epinephrine which requires cortisol 39 Pheochromocytoma tumor of the adrenal medulla which secretes norepinephrine because it is too far from the adrenal cortex Fight or Flight Response 39 Ensures the body can respond appropriately to a stress il situation which includes responses such as increased heart rate cardiac output and blood pressure Parasympathetic Nervous System PARASYMPATH ETIC NERVOUS SYSTEM Circular muscle C l39 l39 Mdbmm EdrngerWestpha I N nary gang Ion commas pUpll quotUC39OUS quot 1 L I i C39IIBWWUSC39O The lIlCtiOIl is to restore to conserve energy 7 39 I CN near VlSIOn Lacnmal nucleus 1 Pons Supcnor salivatory 139r13939 IY inglerygopalaline ganglion Lacnmal and nucleus l nasal glands Inferior salivalory i S 39l nucleus 7 I lt Submandlbular Medulla I quot quot and sublrngual Dorsal motor nucleus 7 glands of vagal nerve quot Parolrd gland Hean Reading Notes Page 30 Stomach Small lnun m Laroe imam Reading Notes Page 31 Lecture 9 Mcnday ct ber 12 Z 15 438 PM Chapter 2 Autonomic Nervous System Autonomic Innervation of the Organ Systems Reciprocal FunctionsSympathetic and Parasympathetic 39 Sympathetic and parasympathetic innervations operate reciprocally or synergistically to produce coordinated responses Sinoatrial Node III Example of coordinated control of function III SA node is the normal pacemaker of the heart and its rate of depolarization sets the overall heart rate III The sympathetic and parasympathetic function reciprocally to modulate the heart rate 9 Increase sympathetic increase heart rate increase parasympathetic decrease heart rate III The sympathetic and parasympathetic actions work synergistically to increase the heart rate Urinary Bladder III Example of reciprocal innervations by sympathetic and parasympathetic divisions III Micturition emptying of the bladder is voluntarily controlled because of the external sphincter which is composed of skeletal muscle III The internal bladder is made of smooth muscle therefore has both sympathetic1umbar spinal cord and parasympatheticsacral spinal cord innervations El When the bladder is lling with urine the sympathetic control predominates When the bladder is full the parasympathetic control predominates emptying of the bladder mountan amorous Control Control a Muscle Slate quot I ansm Stale Scmal cord Ruined Symuthanc Cont acted Palmyan Contracted Sy vameu Relaxed Patasyrrpm Contracted Vountary Relaxed Voum Pupil III Size of the pupil is reciprocally controlled by two muscles of the iris radial muscle controlled by sympathetic innervation through alphal receptors activation causes dilation and the sphincter muscle controlled by parasympathetic innervation through muscarinic receptors activation causes constriction III Pupillary light re ex light strikes the retina and activates the parasympathetic preganglionic nerves causing contraction of sphincter muscle and constriction of the pupil Accommodation response blurred retinal image activates parasympathetic preganglionic neurons which leads to constriction of the pupil III Some organs only have sympathetic innervations such as sweat glands vascular smooth muscle or adipose tissue Coordination of Function Within Organs 39 Recurring physiologic theme that is exquisitely clear III Urinary bladder timely coordination between activity of the detrusor muscle and the sphincters Sympathetic activity dominates when the bladder if lling will simultaneously relaxing the bladder and contracting the sphincter During micturition parasympathetic activity dominates producing contraction of bladder wall and relaxing of sphincter III Gastrointestinal tract contraction of the wall is accompanied by relaxation of the sphincter parasympathetic which allows content to move forward Relaxation of the wall and contraction of the sphincter sympathetic causes a slowing or stopping motion Types of Receptors 39 In parasympathetic division effector organs have only muscarinic receptors 39 In the sympathetic division there are multiple receptor types in effector organs including four adrenoreceptors III In sympathetic cholinergic innervation there are muscarinic receptors Reading Notes Page 32 39 Sympathetic adrenoreceptors receptor type is related to its function El Alpha and alphal receptors cause contraction of smooth muscle III Betal receptors are involved in metabolic functions III BetaZ receptors cause relaxation of smooth muscle Hypothalamic and Brain Stem Centers Hypothalumus r L Tg 3T v r Temperarutc 3 quot7 rrgulalmn V v I u 1 1m Mdbruln 39 Iiij 7 Food Imam l 739 O Responsrble for temperature I L h l T Mmm U m regulation thirst breathing food yr 4 in TN intake micturition and cardiovascular function A F zuxurnu39iuK H39th V095 I I VJSOmOICW DEMO y I C39drdthiiSCUldT I Modmu I 39 Hapmow cmrm 739 Swallowing geegrunt I v vwnllirx centers Spnrmlcu39d It l39 Autonomic Receptors The type of receptor and its mechanism of action determine the nature of the physiologic response which are tissue speci c and cell type specific 0 Beta 1 receptor in the SA node is coupled to mechanisms that increase the spontaneous rate of depolarization and increase the heart rate 0 Beta 1 receptor in ventricular muscle is coupled to mechanisms that increase intracellular Ca2 concentration and contractility The type of receptor predicts which pharmacologic agonists or antagonists will activate it or block it Adrenoreceptors 0 Found in target tissues of the sympathetic nervous system and are activated by the catecholamines norepinephrine and epinephrine O Divided into two types alpha and beta which is further divided into 1 and 2 39 All have a different mechanism of action except for betal and beta2 Responses of Adrenoreceptors to Norepinephrine and Epinephrine 39 There are differences in the responses of alphal betal and beta2 adrenoreceptors to the catecholamines epinephrine and norepinephrine III Norepinephrine and epinephrine slightly more have almost the same potency as alphal receptors Alphal is more insensitive then beta to catecholamines which more higher concentrations is needed to activate alphal receptor This si reached when norepinep hrine is released from postganglionic sympathetic nerve fibers III Norepinephrine and epinephrine are equipotent at betal receptors therefore lower concentration of catecholamines is sufficient to activate betal receptors El Beta2 receptors are preferentially activated by epinephrine when released from adrenal medulla Cholinoreceptors 0 Two types nicotinic and muscarinic 39 Nicotinic receptors are found on the motor end plate in all autonomic ganglia and on the chromaffin cells of the adrenal medulla 39 Muscarinic receptors are found in all effector organs or the parasympathetic division and few in the sympathetic division Reading Notes Page 33
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