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Membrane Potentials. Overview. Introduction Diffusion potentials Nernst equation Donnan membrane equilibrium Resting membrane potential in living cells Action potentials. Introduction. An electric potential (voltage) difference Exists between inside and outside of all cells
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Membrane Potentials Excitable tissues
Overview • Introduction • Diffusion potentials • Nernst equation • Donnan membrane equilibrium • Resting membrane potential in living cells • Action potentials Excitable tissues
Introduction • An electric potential (voltage) difference • Exists between inside and outside of all cells • Trans-membrane potential • Can be measured by • Intracellular recording technique Excitable tissues
Intracellular recording • Microelectrode • Penetrate the membrane • Voltmeter measures • The difference in the distribution of ions • On inside versus the outside Excitable tissues
Intracellular recording Excitable tissues
Resting Membrane Potential • The resting membrane potential • Magnitude varies • 5mv to 100mv • Cell type • Chemical environment Excitable tissues
Resting Membrane Potential • It is approximately • -80mv in excitable cells • Nerves, muscles cells • -20 to -40mv in non-excitable cells • RBC, epithelial cells Excitable tissues
Excitable Cells • Capable of transmitting electrical and chemical impulses • Able to respond to changes in external environment • Leading to change in trans-membrane potential • Develop action potential • Examples: nerve and muscle cells Excitable tissues
Diffusion Potential Hypothetical example • Ions will diffuse from soln 1 to soln 2 • Cl- moves faster than Na+ • Cl- moves ahead of Na+ • Charge separation • Soln 1 will have positive charge • Soln 2 will have negative charge 2 1 0.1 M NaCl 1.0 M NaCl Na+ - + Na+ Na+ Na+Cl- - + Cl- Cl- Cl- - + Excitable tissues
Diffusion Potential Hypothetical example • This is diffusion potential • Depends on movement of ions from one compartment to the other • It is transient • Disappears as soon as equilibrium is attained 2 1 0.1 M NaCl 1.0 M NaCl Na+ - + Na+ Na+ Na+ Cl- - + Cl- Cl- Cl- - + Excitable tissues
Diffusion Potential Hypothetical example • Solution 1 & 2 are • Separated by a semi-permeable membrane • Only K+ can diffuse • K+ will diffuse • Along concentration gradient • From solution 1 to 2 • Charge separation • Solution 1 will have – charge • Solution 2 will have + charge 2 1 0.15 M NaCl 0.15 M KCl K+ + - Na+ K+ Na+ K+ Cl- Cl- Cl- + - Cl- Cl- Na+ Cl- + - -94 mv Excitable tissues
Diffusion Potential Hypothetical example • This is diffusion potential • Depends on movement of ions • From one compartment to another • Magnitude depends • On concentration of K+ in solution 1 2 1 0.15 M NaCl 0.15 M KCl K+ + - Na+ K+ Cl- Na+ K+ Cl- Cl- Cl- + - Cl- Na+ Cl- + - -94 mv Excitable tissues
The Nernst Equation Hypothetical example • The concentration gradient • Which causes the net diffusion of K+ from soln 1 to 2 • Known as • Concentration force • Chemical potential 2 1 0.15 M NaCl 0.15 M KCl K+ + - Na+ K+ Cl- Na+ K+ Cl- Cl- Cl- + - Cl- Na+ Cl- + - -94 mv Excitable tissues
The Nernst Equation Hypothetical example • Given by formula • RTln([K+]1/ [K+]2) • R = gas constant • T = absolute temp • Ln = natural logarithm 2 1 0.15 M NaCl 0.15 M KCl K+ + - Na+ K+ Cl- Na+ K+ Cl- Cl- Cl- + - Cl- Na+ Cl- + - -94 mv Excitable tissues
The Nernst Equation Hypothetical example • The electrical force • Which opposes the diffusion of K+ from soln 1 to 2 • Known as • Electrical potential • Given by formula • EKZF • EK = equilibrium potential for K+ • Z = valence of K+ • F = Faraday’s constant 2 1 0.15 M NaCl 0.15 M KCl K+ + - Na+ K+ Cl- Na+ K+ Cl- Cl- Cl- + - Cl- Na+ Cl- + - -94 mv Excitable tissues
The Nernst Equation • At equilibrium • Electrical force = concentration force • EKZF = RTln([k+]1/[k+]2) • Ek = (RT/ZF) ln([k+]1/[k+]2) • This is Nernst equation • Simplified Nernst equation • Ek = ± 61 log ([K+]1/[K+]2) • Converting to log base 10 • Evaluating (RT/ZF) at 370C • Giving the result in mV Excitable tissues
Living Cells • Transport properties of cell membrane • Na+/K+ pump • Electrogenic pump • 3Na+ out • 2K+ in • Create net deficit of +ve charge inside cell • Inside –ve with respect to outside cell Excitable tissues
Living Cells • Na+/K+ pump also • Cause large conc gradient of Na+ andK+ across the cell membrane • For sodium • 14 mEq/L ICF • 142 mEq/L ECF • For potassium • 140 mEq/L ICF • 4 mEq/L ECF Excitable tissues
Living Cells • Leakage of K+ and Na+ through • Channel proteins • K+/ Na+ leak channels • Channels are more permeable to K+ than to Na+ Excitable tissues
The Living Cells • Living cells are bound by cell membrane • Ionic composition of ICF differs from that of ECF • Cell membrane • more permeable to K+ • Na+ can permeate with difficulty • Effectively kept out by the Na+/K+ pump • Cl- kept out because • The –ve charges of impermeate anions • Thus K+ diffuse out along concentration gradient Excitable tissues
The Living Cells • K+ diffuse out of the cell • Create a diffusion potential • Magnitude of potential given by the Nernst Equation • Ek = (RT/ZF) ln([K+]1/[K+]2) • = - 61log (140/4) • = - 61 log 35 • = -61 x 1.54 mv • = - 94 mv Excitable tissues
The Living Cells • Equilibrium potential for Na+ would be • ENa = - 61log (14/142) • = - 61 log (1/10) • = + 61 mv Excitable tissues
The Living Cells • The measured resting membrane potential is about • -85 mv in muscles and -70mv for nerves • The reason for this deviation • Membrane is not completely impermeable to Na+ • Na+ tend to move into cell along conc gradient • Reduces the magnitude of negative charge inside Excitable tissues
Goldman Equation • The magnitude of the resting membrane potential at any given time is dependent on • Distribution of K+, Na+ and Cl- • Permeability of the membrane to these ions Excitable tissues
Goldman Equation • Given by the following equation • V = (RT/F) {(pK[k+]o/ pK[k+]i) + (pNa[Na+]o/ pNa[Na+]i) + (pCl[Cl-]i/ pCl[Cl-]o)} • pK+ = permeability of potassium ion • pNa+ = permeability of sodium ion • pCl- = permeability of chloride ions Excitable tissues
The action Potential • The RMP is • -70 mv in nerve cells • -85 in muscle cells • If the cells are disturbed (stimulated) • Rapid change occur in membrane pot from • -70 mv to + 30 mv then • Back to -70mv Excitable tissues
The action Potential • This rapid changes in membrane potential • Known as Action Potential (AP) • Duration of AP • 1 msec in nerve • 10 msec in muscle • 200 to 300 msec in cardiac Excitable tissues
Ionic Bases of Action Potential • Resting membrane is 50 to 100 times more permeable to K+ than it is to Na+ • RMP is closer to K+ equilibrium potential than it is to Na+ equilibrium potential Excitable tissues
Equilibrium Potentials Na+ Equilibrium Potential + 61 mV Zero Potential 0 mV Resting Membrane Potential - 84 mV - 94 mV K+ Equilibrium Potential Excitable tissues
Ionic Bases of Action Potential • On stimulation • Permeability of membrane to K+ and Na+ changes • Both K+ and Na+ permeability increases • Na+ permeability increases much more than that for K+ Excitable tissues
Depolarization • Stimulation causes • Voltage gated Na+ channels to open • Na+ diffuse into cell • Entry of +ve charges • Membrane pot to become +ve Excitable tissues
Depolarization • Inside become +ve relative to outside • Depolarization phase • Na+ gates open • Brief moment • Then they close Excitable tissues
Re-polarization • The voltage changes occurring during depolarization cause • Voltage gated K+ channels to open • K+ diffuse out Excitable tissues
Re-polarization • Exit of K+ causes • Membrane pot to become –ve • The inside once again • Become –ve relative to outside • Repolarization Excitable tissues
Action Potential • Depolarization • Na+ channels open • Na+ diffuse IN • Repolarization • Na+ channels close • K+ open • K+ diffuse out Excitable tissues
Action Potential • Point A • Resting phase • Na+ and K+ channels closed • Point B • Depolarization • N+ channels open • K+ channels still closed Excitable tissues
Action Potential • Point C • Repolarization • Na+ channels closed • K+ channels open • Point D • Hyper-polarization • K+ channels remain open longer time Excitable tissues
Silverthorn: Textbook of Physiology Excitable tissues
Threshold Stimulus • Action potential occur only when the membrane is stimulated enough • To cause Na+ channels to open • The minimum stimulus needed • To achieve an action potential is called • The threshold stimulus Excitable tissues
Threshold Stimulus • Sub-threshold stimulus causes • Membrane potential to become less negative • No matter how small the stimulus is • Causes few Na+ channels to open • Na+ move inside (positive feedback effect) Excitable tissues
Threshold Stimulus • If the membrane potential reaches the threshold potential (generally 5 – 15 mV less negative than the RMP) • Enough voltage gated Na+ channels open causing • Influx of Na+ into the cell • Depolarization occurs Excitable tissues
Absolute Refractory Period • During action potential (AP) • Second stimulus will not produce another AP no matter how strong the stimulus is • Corresponds to the time when the Na+ channels are open ( few msec) Absolute refractory period Relative refractory period Excitable tissues
Relative Refractory Period • During this period • Another AP can be produced • Using stimulus greater than the threshold stimulus • Corresponds to the period when the K+ channels are open Absolute refractory period Relative refractory period Excitable tissues
Spread of Action Potential • In un-myelinated nerve • AP elicited on one portion • Usually excite adjacent portion • Local current flow • Active region stimulate adjacent inactive region Excitable tissues
Spread of Action Potential • AP is conducted • Away from stimulus point • From one region to another Excitable tissues
Saltatory Conduction • Myelin sheath wrap around the nerve to form an insulator • At nodes of Ranvier there is no myelin • RMP and AP are generated at the nodes Excitable tissues
Saltatory Conduction • When the fibre is depolarized • Only the nodes become active • Local current flow from active node through the ICF to the inactive node • And through the ECF from inactive to active Excitable tissues
Saltatory Conduction • The outward flow of current at the inactive node depolarizes the membrane • Excitation jumps from one node to another • This is known as saltatory conduction Excitable tissues