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Transcript
Mammalian Physiology Resting Membrane Potentials Action Potentials UNLV UNIVERSITY OF NEVADA LAS VEGAS PHYSIOLOGY, Chapter 2 & 3 Berne, Levy, Koeppen, Stanton Objectives • • • • • Describe the basics of electrophysiology Describe the ionic basis of the resting membrane potential Describe the ion movements in an action potential Describe factors determining conduction velocity Describe the function of the myelin sheath Basic Concepts • Ohm’s Law I= E R – I = current – movement of electrical charge – E = voltage – electrical potential (difference in charge between 2 points) – R = resistance – hindrance to charge movement • • High electrical resistance – insulators Low electrical resistance – conductors Basic Concepts • Resting membrane potential – Difference in ion concentration • Current carried by Na+ and K+ – Difference in membrane permeability • Selectively permeable membrane responsible for potential difference • RMP represents a charge or voltage difference across the membrane • Permeability changes with electrical activity • Excitable cells – nerve cells, muscle cells Basic Concepts Separation of charge is defined as potential energy (the potential to do work), thus this separation of charge is termed “membrane potential” or Voltage and in cells is measured in millivolts (mV). If the charge is allowed to move across the membrane then the potential energy is turned into work, thus when ions or electricity flows you have “current” flow. If something slows or hinders the flow of ions or electricity this is termed “resistance” Typical Ion Distribution Concentration of Ions (mmols/liter) Ion Na+ ClK+ Extracellular 150 110 5 Intracellular 15 10 150 Equilibrium Potential • • Consider forces acting on ions – electrical charges & concentration gradients Membrane is selectively permeable – K+ is freely permeable – Na+ is relatively impermeable • • • • • K+ - driving force down concentration gradient out of cell – seeks chemical equilibrium Impermeable negatively charged anions exert electrical force on K+ tending to keep K+ inside the cell Resting membrane potential is established when inward electrical gradient for K+ is balanced by outward chemical gradient for K+ When these forces balance – no net K+ movement Equilibrium constants for ions can be calculated by Nernst equation - Keq Cell Membrane Outside Inside Na+ Na+ [150] [15] K+ K+ [5] [150] Cl- Cl- [110] [10] Cell Membrane Anions - Na/K ATPase pump Nernst Equation • Nernst equation can be used to predict direction of ion flow – If measured potential = calculated potential, ion is in equilibrium and no net ion flow occurs – If measured potential is same sign as calculated potential, but larger, electrical force is greater than chemical force and ions will flow in direction of electrical force – If measured potential is same sign as calculated potential, but less, chemical force is greater than electrical force and ions will follow chemical force – If measured potential is opposite sign than calculated potential, electrical and chemical forces are in the same direction – ion cannot be in equilibrium Nernst Equation Chemical forces acting on an ion = RT ln [A]/[B] Electrical force acting on an ion = zF(EA– EB) At equilibrium, RT ln[A]/[B] + zF(EA– EB) = 0 or (EA – EB) = RT ln[B] converting to log10 and standardizing for RT (2.303 RT/F = 60 mv) zF [A] EA – EB = -60 mv log [A]I z [B]o (equation 2-4) Nernst Example Keq = -60 log [0.1] 1 [0.01] = -60 log 10 = -60 mv General rule: An electrical potential difference of 60 mv is needed to balance a 10 fold concentration difference Nernst Example K+o = 5 meq K+I = 150 meq Na+o = 150 meq Na+I = 15 meq Keq = ? Keq = -60 log [150] [5] = -60 log 30 = -60 x 1.5 = -90 mv K+ Keq = -60 log [15] [150] = -60 log 0.1 = -60 x -1 = +60 mv Na+ -90 mv is resting membrane potential of excitable cells So, resting membrane potential is a result of K+ permeability Resting Membrane Potential • • • • • K+ permeability allows K+ to follow concentration gradient There is some Na+ leakage into the cell – enough to raise Keq to -70 mv This would be expected to cause K+ to leave the cell (RMP<Keq for K+) If not checked, K+ and Na+ would both reach chemical and electrical equilibrium Na/K ATPase pump maintains concentration gradient – Electrogenic pump (3 Na out/2 K in) An Action Potential Action Potential is a brief reversal of membrane potential polarity due to changes in ion permeability when cell is depolarized to threshold Action Potentials Action potentials from different cell types have different durations Characteristics of Action Potential • • Threshold is 10-15 mV depolarized (ie. –55 to –60 mV) All or none response – Once membrane reaches threshold, amplitude is independent of strength of initiating stimulus – Action potential cannot be summed • • • • Nerve has a refractory period – period when a subsequent stimulus will not generate another action potential Action potential is conducted without decrement (amplitude is constant) Duration of action potential is constant Signaling is accomplished by changing frequency of action potentials Action Potential • • • • • When membrane potential is raised to threshold, voltage-gated Na+ channels open and Na+ enters cells following electrical and chemical gradients As inside of cell becomes positive, K+ efflux increases and Na+ entry slows (K+ voltage-gated channels open, increasing K+ efflux) As positive charges leave cell, potential returns toward 0 and voltage-gated Na+ channels close while K+ channels remain open; Na+ entry ceases while K+ efflux continues Slow closure of K+ voltage-gated channels leads to overshoot Resting membrane potential is restored by Na/K ATPase pump Ion Conductance in an Action Potential Action potential is sum of Na+ and K+ conductances – note the differential time course of ion movement Action Potential Summary Refractory Period Action potential moves from the initial area of depolarization outward, not back toward the center due to the inactive state of the voltage-gated Na+ channels Electrotonic Conduction Action is propagated by cycles of depolarization – depolarization of membrane generates an action potential, producing local currents which bring adjacent regions to threshold, generating action potentials which produce local currents which bring adjacent regions to threshold….etc. Conduction Velocity • • • • • Conduction velocity is determined by membrane capacitance (Cm) and electrical resistance to current flow Membrane potential is the charge stored by the membrane capacitor Membrane capacitance is the amount of charge that must flow to depolarize the membrane The larger the capacitance, the greater the amount of charge that must flow and the slower the conduction velocity Capacitance is a function of the membrane surface area that must be depolarized Conduction Velocity • • Electrical resistance determines how rapidly charge can flow Resistance to current flow is a function of resistance to current flow across the membrane (Rm) and resistance to current flow along the cytoplasm of the nerve (Rin) – Currents that flow across the membrane are lost from the cable – Currents that flow through the longitudinal resistance carry the signal along the cable The effective resistance is proportional to the geometric mean of Rm and Rin Rm·Rin Fiber Size and Conduction Velocity Time constant for conduction is Cm x Conduction velocity = Cm x Rm · Rin 1 Rm · Rin Nerve or muscle cell can be viewed as a cylinder Surface area = 2π·r·l Cross-sectional area = π r2 Capacitance (Cm) is proportional to surface area Membrane resistance (Rm) is inversely proportional to surface area Internal resistance (Rin) is inversely proportional to cross-sectional area Doubling of nerve radius will increase Cm by 2, decrease Rm by 2 and decrease Rin by 4, so product of Cm x Rm · Rin = 2 x 1 = 1 2x4 2 This means conduction velocity increases by a factor of 2 when radius doubles Conclusion: larger fibers have faster conduction velocities Myelin Sheath Schwann Cells: -in the PNS Schwann cells myelinate axons which greatly increases conduction velocity -Schwann cell plasma membranes are lipid dense and wrap around the axon to form the myelin sheath -Schwann cells wrap themselves around the axon at regular intervals leaving gaps or bare spots on the axon called “Nodes of Ranvier” Myelin Sheath and Conduction Velocity • • Myelin sheath increases conduction velocity without increasing nerve size Increases length constant of nerve – Increases Rm by blocking current flow across membrane – Ratio of Rm/Rin is greater – Less dilution of ions across large membrane area • Decreases capacitance of membrane – Myelin sheath decreases surface area that must be depolarized • Restricts generation of action potentials to nodes of Ranvier – Na+ and K+ are concentrated at isolated sites Myelin Sheath and Conduction Velocity Myelinated axons have greater conduction velocities than unmyelinated nerves with100 times diameter 10 µm myelinated fiber = 50 m/sec 500 µm unmyelinated fiber = 25 m/sec Saltatory Conduction The action potential appears to jump from node of Ranvier to node of Ranvier. Only the membrane at the node of Ranvier depolarizes, not the membrane under the myelin sheath. There are no ion channels under the myelin sheath. The jumping or saltatory conduction is much faster than depolarizing the entire membrane. Action potential doesn’t really jump – rather ions accumulate at nodes of Ranvier – increased conductance – build-up of ions means faster movement of ions across membrane = faster signal conduction