Week 1 Reading Notes
Week 1 Reading Notes Bio Sci E109
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Bio Sci E109
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This 12 page Class Notes was uploaded by Muni Notetaker on Monday September 28, 2015. The Class Notes belongs to Bio Sci E109 at University of California - Irvine taught by LOUDON, C. in Summer 2015. Since its upload, it has received 43 views. For similar materials see HUMAN PHYSIOLOGY in Biology at University of California - Irvine.
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Date Created: 09/28/15
Lecture 2 Reading 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 minermeniam of carriermediated transport E quotElEW fa e y and solute concentration 3 FleaH 5 Equot fquot Low solute concentrations E l Elmme IIquot yquot gamma increase transport rates and I HIP III39 Equot concentration increases II High solute concentration 39 transport rate levels off likllti ill39 l aijull 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 a Net d1ffus10n reater movement of E3 Q Q 3 g 1 molecules from A to R then R to A Reading Notes Page 1 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 2 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 3 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 4 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 5 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 6 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 1 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 2 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 2 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 3 4 Clquot ent 01 1 negatlve Reading Notes Page 4 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 1 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 2
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