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Membrane potential Potential difference (voltage) across the cell membrane. In all cells of the body (excitable and nonexcitable). Caused by ion concentration differences between intracellular and extracellular fluid. Membrane potential caused by diffusion of ions 142 mM 4 mM 140 mM 14 mM Nernst potential Nernst equation (37°C, for univalent ions): ± 61 log Concentration inside (mV) Concentration outside For each ion proportional to ratio of concentrations inside and outside the cell. Always expressed as extracellular fluid has potential zero, and Nernst potential that from inside the cell. Diffusion potential The membrane is permeable to several different ions at the same time! Goldman equation: Em = - 61 log CNaiPNa + CKiPK + CCliPCl (mV) CNaoCNa + CKoPK + CCloPCl (C) Concentration (P) Membrane permeability Em = PK Ptot EeqK+ PNa Ptot PCl EeqNa+ Ptot EeqCl Membrane permeability for K+ and Na+ (resting state) In resting nerve cells – open potassium ”leak” channels (“tandem pore domain”). 100x more permeable for K+ than Na+. outside Origin of Resting Membrane Potential Contribution of Na+/K+ pump Maintenance of concentration gradients for K+ and Na+ across cell membranes. Electrogenic: creates additional negativity ~4 mV. Measurement of membrane potential Nerve Action Potential Voltage-gated Na+ channels 1. 2. 3. Voltage gated K+ channels K+ leak channels Na+/K+ pump Voltage-gated Na+ and K+ channels Action Potential Role of Ca2+ c(Cai)=10-7 mol/l c(Cao)= 10-3 mol/l Strong concentration gradient (10 000-fold concentration difference) In resting state, permeability for Ca2+ negligable. In heart cells, voltage-gated Ca2+ channels participate in action potential (plateau). Action potential with plateau (heart) Initiation of action potentials Action potentials will not discharge until there is appropriate stimulus – depolarization. Exception – spontaneous rhythmicity. Stimulus can be mechanical (mechanoreceptors), chemical (neurotransmitters) or electrical (heart muscle). Positive feedback opens more and more Na+ channels. Initiation of action potentials “Acute local potentials” must reach threshold for eliciting AP “all or nothing” phenomenon. Refractory Period Period of decreased excitability (relative r.p.) or complete inexcitability (absolute r.p.)during and after action potential. mV Rhythmicity of Excitable Tissues Repeated spontaneous rhythmical discharges (no outside stimulus). Heart (SA-node rhythmic activity), intestinal smooth muscle (perystalsis) i CNS (breathing pace-maker). Other excitable tissues can spontaneously discharge if threshold is lowered. Spontaneous rhythmicity Resting membrane potential -60 do -70 mV (close to threshold) activation Na + and Ca2+ channels. Depolarizationa activates slow K+ channels repolarization i hyperpolarization. Propagation of action potentials Myelinated nerve fibers Myelin sheath: Insulation Decreases membrane capacity every 1-2 mm along axon myelin sheath is interrupted prekid mijelinske ovojnice Ranvier nodes 2-3 μm in length. Saltatory conduction Action potential are generated only in nodes of Ranvier energy saving and faster conduction (100 m/s). Non-myelinated fibers conduction velocity 0,25 m/s.