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BSC 300, Week 5

by: Ashley Bartolomeo

BSC 300, Week 5 BSC 300

Ashley Bartolomeo
GPA 3.9

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Notes on chapter 4 part 2, membrane structure and nerve impulses
Cell Biology
John yoder
Class Notes
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This 6 page Class Notes was uploaded by Ashley Bartolomeo on Friday September 16, 2016. The Class Notes belongs to BSC 300 at University of Alabama - Tuscaloosa taught by John yoder in Fall 2016. Since its upload, it has received 3 views. For similar materials see Cell Biology in Biology at University of Alabama - Tuscaloosa.


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Date Created: 09/16/16
Chapter 4 Movement of Substances Across Cell Membranes Key Concepts  Describe mechanisms for transporting materials across membranes o Passive diffusion: simple and facilitated diffusion o Active transport  Resting membrane potential  Action potential and nerve pulse  Synaptic transmission Movement of Substances Across Cell Membranes  Diffusion – spontaneous process in which a substance moves from area of high concentration to area of low concentration until equilibrium is reached (down their concentration gradient)  Permeability is the property of a membrane to allow substances to diffuse across the membrane: polarity, size, concentration and charge  Polarity: more hydrophobic, the faster the diffusing rate  Size: large molecules, like proteins, are physically blocked from diffusing across biological membranes  Concentration: molecules cannot diffuse against their concentration gradient by simple diffusion  Charge: ionic and polar molecules (electrolytes). The combination of concentration and charge constitutes an electrochemical gradient. Solute charge can dramatically alter permeability  Without considering a solute charge, the free energy change of diffusion is strictly concentration dependent: G = RT ln [Ci] / [Co]  G = 1.4 kcal/mol log10 [Ci] / [Co]  For a solute that is 10 times higher outside of the cell than inside, the free energy change would be G = -1.4 kcal/mol  For electrolytes however, we must also consider the solute charge and the voltage across the membrane, that is, the membrane’s electrical potential, which is typically about -70mV (meaning there is a large negative charge inside of the cell)  For charged solutes, consider a 10 molar excess of Na+ outside the cell: o G = RT ln [Ci] / [Co] + zFEm  G = -1.4 kcal/mol + (1)(23.06) (-.07) o G = -3.1 kcal/mol o F is the Faraday constant (23.06 kcal/V x mol) o Z is the electrolyte charge (Na+ = +1) o Em is the membrane potential (-70 mV = -.07 V), reflecting a difference in charge across the membrane (the cytoplasmic side of the membrane is more negatively charged)  Don’t worry about memorizing these values, but recognize that solute charge will either increase or decrease its diffusion potential Cell Membranes Are Selectively Permeable  Membrane traffic is highly regulated allowing for separation and exchange of materials  Solute movement can occur by passive diffusion or active transport  Passive diffusion is movement down the solute gradient and is spontaneous  Active transport is against solute gradient and requires energy  Cells are capable of regulating traffic across their membranes, controlling both import and export Membrane Permeability Can Result from Either:  Simple diffusion: the solute being small enough to pass through the membrane (between the lipids). Water, though polar, is small enough to readily diffuse across membranes, but not as well as small non-polar molecules like O2 or CO2  Facilitated diffusion: due to size or charge exclusion, protein channels that span biological membranes are often deployed. These can be tightly regulated in order to control permeability and are highly specific to the solute diffusion down its concentration gradient  These both represent passive diffusion, movement of solutes down their concentration or electrochemical gradient Osmosis: A Special Case of Passive Diffusion  Osmosis: diffusion of water through a semipermeable membrane  Because membranes are permeable to water, but not ions, water diffuses from side of lower electrolyte concentration to side of higher concentration  Cells swell in hypotonic solution  Cells shrink in hypertonic solutions  Remain unchanged in isotonic solutions Aquaporin Allows Passive Diffusion of Water  Some cells absorb water at a much higher rate than simple osmosis predicts  For example, kidney cells must reabsorb a significant amount of water during producing urine  Such cells are equipped with a water-specific channel protein called aquaporin that allows diffusion of over 10^9 water molecules per second  The protein is so selective that not even hydrogen atoms can tag along for the ride  This Nobel prize winning discovery may have therapeutic potentials The Diffusion of Ions Through Membranes  Rapid movement of ions across membrane (conductance) is critical to many cell processes: nerve impulses, muscle contraction, release of signaling molecules into cell cytoplasm etc.…  Electrical charge of ions makes them repulsive to the hydrophobic core of the bilayer: they cannot diffuse across a membrane  Ions must cross through gated ion channels  Highly selective and bidirectional, allowing diffusion in the direction of the electrochemical gradient  Voltage gated: Na+, K+, Ca2+, Cl- channel family  Ligand gated: AchR, binds to protein channels and opens it  Mechano gated: convert mechanical cues to biochemical signals Facilitated Diffusion  Large, polar or ionic substances require a facilitative transporter to cross membranes passively  Facilitative diffusion is passive, specific and highly regulated  The direction of solute movement depends on the concentration and could be reversible, which is different from the transporters involved in active transport The Glucose Transporter: An Example of Facilitated Diffusion  Increased blood glucose levels stimulate secretion of the hormone insulin by pancreatic b-cells  Insulin responding cells quickly integrate the glucose transporter into their membranes  Glucose binds the transporter leading to a change in conformation that allows glucose o be released into the cell interior  In the first step of glycolysis, phosphorylation of glucose in the cytoplasm maintains a high extracellular glucose concentration Active Transport  Endergonic process that moves molecules against their concentration gradient o Maintains gradients for potassium, sodium, calcium and other ions across the cell membrane o Couples movement of substances against gradients to exergonic processes, like ATP hydrolysis, the absorbance of light, or the flow of other substances down their concentration gradient Primary Active Transport Coupled to ATP Hydrolysis The Sodium-Potassium Pump (Na+/K+ ATPase)  Na+/K+ ATPase moves 3 Na+ ions out and 2 K+ ions into the cell, thus, generating a steep Na+ and K+ gradient across the cell membrane  The ion gradient is used for forming action potential in nerve cells and initiating contractions in skeletal muscle cells  The ion gradient could serve as energy source to stimulate the movement of other molecules  Its importance to cell physiology is reflected by the fact that 1/3 of all cellular ATP of most cells is used to drive this pump (2/3 in nerve cells)  It’s a P-type pump: phosphorylation causes change in conformation and ion affinity that allow transport against gradients  Couples ATP hydrolysis to ion transport  In its resting state, bound to ATP, the pump is open to cell interior and has high affinity for 3 Na+ ions, binding alters the pump’s conformation  ATP is hydrolyzed and the phosphate group transferred to a residue on the pump – which again alters the conformation of the pump  In this conformation, the pump has little affinity for Na+ but strong affinity for K+. the Na+ are released and 2 K+ are bound  This causes dephosphorylation and again alters the pump’s conformation to its original state with high affinity for Na+ and low affinity for K+  The K+ is released to the cell interior and ATP binds the pump again Other Primary Active Transport Systems  Diverse number of P-type pumps that include H+, Ca2+ and H+/K+ ATPases  The H+/K+ ATPase responds to food consumption by pumping H+ ions into the stomach  Acid neutralizing drugs like Prilosec inhibit the pump itself, or other like Zantac block receptors that lead to pump activation ABC Transporters  ABC = ATP binding cassette  Large diverse family  Share characteristic core structure o Two transmembrane domains o Two cytosolic ATP binding domains  Each transporter is specific for single substrate or small group  Mutation of one ABC transporter, CFTR, is responsible for Cystic fibrosis Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)  CFTR is a peculiar ABC transporter in that it no longer functions in active transport, but instead is a passive cyclic AMP-regulated Chloride channel, not a transporter  CFTR allows Cl- ions to diffuse out of epithelial cells in the lungs, liver, pancreas, digestive tract, reproductive tract  Activated CFTR suppresses the activity of epithelial Na+ channel. The resulting osmotic gradient secretes water into the lumen  The water lowers the viscosity of secreted mucus and allows infections bacteria to be cleared Cystic Fibrosis – Cause  In the absence of the CFTR protein, decreased Cl- and increased Na+/H2O reabsorption lead to dehydration of mucus layer  Pathogenic bacteria cannot be cleared  The majority of the CF patients die due to respiratory failure  Majority of CF cases result from a single point mutation that prevents the protein from folding correctly – and it therefore never reaches the cell membrane (F508 mutation – eliminates a single amino acid)  Clinical trials using stealth liposomes to deliver normal copies of the gene are underway  Fire report (2015, Lancet) of 136 patients receiving a yearlong regimen of inhaled liposome – CFTR showed modest, but significant improvement in lung function Using Light Energy to Actively Transport ions  Some archaebacterial use a protein called bacteriorhodopsin, which absorbs light energy to transport protons out of the cell  The proton gradient is used to make ATP Secondary Active Transport, aka Cotransport  Established solute gradients can be used as an energy source to power cotransport  Example: The Na+/K+ ATPase keeps intracellular Na+ levels low  Intestinal epithelial cells sequester Na+/K+ ATP to the basal cell region  While another transporter – the Na+/glucose cotransporter is localized to the apical surface facing the lumen of the gut  Other cotransport systems move solutes in opposite direction and therefore are termed antiporters, or exchangers  For example, many cell types maintain appropriate pH by coupling Na+ facilitated diffusion with H+ export  Secondary transporter: The Na+ gradient helps to transport glucose by a Na+/glucose co-transporter Nerve Cells Communicate Through Electric Impulses  Cell membrane is negatively charged, the membrane potential is between -15 and -100 mV (negative inside)  The membrane potential of unexcitable nerve or muscle cells is around -70 mV (resting potential), mainly determined by K+ leak channels Voltage Gated K+ Channels  Eukaryotic voltage gated K+ channel is a homotetramer  Each subunit has six transmembrane helices, including a pore domain and a voltage sensing domain  The voltage gated K+ channel could be present in an open/inactivated/close configuration due to the protein conformational change  The inactivated status of voltage gated channels limit the period of time the channels remain open, which ensure the nerve pulse is propagated in one direction along the axon The Action Potential  Threshold: the level of depolarization needed to trigger an action potential (-50 mV), which is used to open the voltage gated Na+ channel  Rising phase: voltage gated Na+ channel open, Na+ ions flow in  Falling phase: voltage gated K+ channel open, K+ ions flow out; Na+ channel inactivated The Propagation of Action Potential  The mechanism of the refractory period: Na+ channel inactivation; hyperpolarization by increased permeability of K+ ions  An action potential is an all-or-none event Synaptic Neurotransmission  Synapse is the junction between the nerve cells and their target cell  A synapse connects a motor neuron and a skeletal muscle cell is called neuromuscular junction  A chemical substance (neurotransmitter) could transmit either excitatory or inhibitory signals across the synapse  A neurotransmitter could transmit either excitatory or inhibitory signals across synapse, which depends on the receptors on the postsynaptic membrane  AchR is a ligand gated Na+ channel, the opening of AchR triggers the depolarization of postsynaptic membrane (excitatory signal)


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