9:17 Membrane Electrophysiology PDF

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System Name: FMS 2 – Physiology Lecture Name: Membrane Electrophysiology Lecture Date: 9/17 Exam Date: 10/30 Distinguish between net flux and unidirectional flux, voltage difference due to ion flux Electrochemical Equilibrium  Most animal cells have an electrochemical potential of 40-100 millivolts across plasma membranes  Usually negative potential within cell relative to extracellular fluid  Net diffusion of ions from higher concentration to lower concentration proportional to concentration difference  Net flux – when concentration of ions is equal on both sides, ions still move but no net movement  Unidirectional flux – the movement of one ion in one direction, will happen in both directions  Voltage difference – proportional to rate of ion movement between both sides o Causes a driving force for ions to move o Arise b/c ions move across membrane at different rates  Driving force – force that drives ions to move due to concentration + voltage differences o Even if driving force is the same for Na+ and Cl- b/c of concentration differences, ions diffuse at different rates o Different diffusion rates b/c of the size of the hydrated ions o Hydrated chlorine smaller than hydrated sodium ∴ smaller frictional resistance moving through water  Side that Cl- moves to will become electronegative, slow down Cl- movement and speed up Na+ movement. As Na+ catches up, Cl- starts to move faster until ions are balanced  As this happens, voltage difference decreases in magnitude and ions move towards concentration equilibrium. o Transport proteins – also help determine rates of movement across membrane  Electrochemical equilibrium - net force of ion is 0 b/c forces equal o May still have a concentration difference in the ion, but this concentration difference maintained by equal but opposite voltage difference o Just b/c forces are equal does not mean concentrations are the same o Concentrations of ions do not change  Equilibrium potential difference – voltage difference that prevents a change in concentration difference for an ion across a membrane  Electrochemical potential = chemical potential + electrical potential  Membrane potential – differences in ion concentration across a cell membrane which cause a voltage difference o Resting membrane potential ranges from -40mV to -100mV o Weighted average of the equilibrium potentials described by the Nernst equation for each ion o Ions that move faster make a larger contribution to the membrane potential no matter the mechanism of transport o Extremely small # ion movement – causes large changes in membrane potential Describe the relationship between the Nernst Equation and the equilibrium potential Nernst Equation  The equation that expresses the balance between the electrical + chemical driving forces  (RT/ZF) ln (Cout/Cin) = Vin – Vout = E o 60/z log (Cout/Cin) = Vin – Vout = E  Electrical potential difference (V) balanced w/ driving force due to concentration differences (C) for an ion  Vout – grounded at zero potential ∴ equation yields magnitude and sign of electrical potential inside the cell required to maintain the concentration difference  Deals w/ only 1 ion at a time with a valence (z)  RT/F = 25mV at room temperature  Equilibrium potential for an ion (Ei) = electrical energy equivalent of chemical energy stored in concentration gradient  Equilibrium potential Na+ = +62mV  Equilibrium potential K+ = -89mV  Equilibrium potential Cl- = -81mV Understand and explain the chord conductance equation Chord Conductance  Conductance (g) – rate of ion

movement across cell membranes is proportional to the membrane conductance for each ion o Determined by transport proteins embedded in cell membrane  Chord conductance equation – o Denominator represents total conductance of membrane to all ions o E represents Nernst (equilibrium) potential for each ion o Value of conductance for each ion relative to total conductance of the membrane determines how much weight is given to equilibrium potential for that ion o If relative conductance of Na+ were suddenly ton increase dramatically (0.9) the membrane potential would be driven towards ENa or ECl. o Changes in ion conductance occur when ion channels open/close or when # channels in plasma membrane changes o Resting membrane potential – closely matches potassium b/c potassium conductance is higher than conductance of other ions Describe the physiological consequences at the cellular level of Na/K-ATPase transport activity Na+/K+ ATPase  Transports Na+ out of cell, transports K+ out  Balances passive tendency for ions to diffuse to their equilibrium concentrations  Hydrolyzes ATP  converts chemical energy into potential energy in the form of a sodium gradient across the plasma membrane Draw a diagram of a simple epithelium. Label the different fluid compartments on each side of the epithelium and the location of the Na/K ATPase. Distinguish between transcellular epithelial transport and paracellular epithelial transport Membrane Transport mechanisms  Carrier mediated transport – mediated by membrane proteins, all important solute movement  Passive biological transport – transport with concentration/voltage differences, transport glucose  Primary active transport – use ATP hydrolysis directly, away from electrochemical equilibrium o Na/K ATPase  Secondary active transport – sodium-solute cotransport proteins, use potential energy in gradient for transport o Symport – transport two items in same direction (sodium + glucose) o Antiport – transport two items in opposite direction (Na/K) o Couple thermodynamically unfavorable rxn with a thermodynamically favorable one  Transporters – use alternate access transport, can be closed, or open only intracellularly or extracellularly o Only one gate can be open at once o GLUT transporters  Ion channels – voltage or ligand gated Na/K ATPase – AKA sodium pump (electrogenic b/c maintain negative resting potential in cell)  Na+ passively leaks into cells, K+ passively leaks out of cells  Complete inhibition results in death  Pump 3 Na+ out, 2 K+ in  Stores energy from ATP hydrolysis by maintaining sodium gradient  Inhibited by cardiac glycosides (digitalis/ouabain) – small clinical range b/c arrhythmias can occur o Treat congestive heart failure + some arrhythmias  There are other types of ATPases Epithelia  Caption: Simple epithelium w/ brush border membrane at the apical (luminal) surface which is in contact w/ interior of hollow organs (intestine/renal tubule). Serosal surface in contact w/ blood vessels. Smooth muscle layers on mucosal surface of epithelium. Individual epithelial cells connected by tight junctions that contain claudins + occludin. Different transport proteins located in apical + basolateral membranes leading to vectoral transport across epithelium

Na/K ATPase – only in basolateral membrane Transcellular pathway – across the cell o Molecule passes through apical/luminal cell membrane (external environment) or brush border/mucosal surface  basal/lateral cell membranes (supported by basement membrane or in contact w/ interstitial fluid/ serosal surface)  Paracellular pathway – next to cells o Molecule penetrates tight junction + diffuses through lateral intercellular space between adjacent cells o Claudins – determine which ions can move between cells by paracellular route  Primary driving force for net solute absorption/secretion across epithelial barriers = active transport of Na+ by Na/K ATPase in basolateral membrane of epithelial cell  Transepithelial secretion of K+ by Na/K ATP-ase o Apical transporters/channels use transmembrane gradients created by pump o Absorb Na, secrete K+ Describe the regulatory volume decrease and regulatory volume increase responses of cells when exposed to hypotonic and hypertonic solutions Coupling Solute Movement w/ Water movement  Concentration of pure water = 55 molar, if solute added concentration of water decreased and solute concentration increased  Water follows solute to maintain equilibrium (osmosis) o Happens very quickly ∴ water at osmotic equilibrium across most cell membranes  For every mOsmoles of solute that moves across membrane, 190 mOsmoles of water must also move to maintain osmotic equilibrium  1 molar concentration of NaCl = 2 Osmolar concentration of Na+/Cl- ions b/c ions behave independently  Isotonic – do not cause change in volume of cells  Hypotonic – less than 290 mOsmoles/L of impermeable solutes  cells swell as water enters  Hypertonic – more than 290 mOsmoles/L of impermeable solutes  cells shrink as water leaves  Tonicity does not equal osmolarity b/c of permeable ions which only have temporary transient effects on cell volume Regulatory Volume  Osmotic concentration of cells = 290mOsmols/L  Steady state volume – determined only by concentration of solutes like sodium which are unable to reach equilibrium due to active transport  No change in cell volume w/ NaCl b/c Na/K ATP ase prevents sodium from reaching equilibrium  Urea  cells shrink o Transient effect b/c permeable  Regulatory volume decrease – in hypotonic solution, allow for passive diffusion of K+ and an anion o If cell swells, water removed w/ ion transport tout o If cell shrinks, water brought in w/ ions o Hypotonic - ⬆ K+/Cl- efflux from cell o Hypertonic - ⬆ Na+/Cl- influx from cell  ...