2. Membrane potential  Potential difference (voltage) across the cell membrane.  In all cells of the body (excitable and non- excitable).  Caused by ion concentration differences between intracellular and extracellular fluid.

3. Membrane potential caused by diffusion of ions 4 mM 140 mM 142 mM 14 mM

4. Nernst potential ratio of concentrations  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. ± 61 log Concentration inside Concentration outside (mV)  Nernst equation (37°C, for univalent ions):

5. Diffusion potential  The membrane is permeable to several different ions at the same time!  Goldman equation: Em = - 61 log C Na i P Na + C K i P K + C Cl i P Cl (mV) C Na o C Na + C K o P K + C Cl o P Cl (C) Concentration (P) Membrane permeability Em = P K P Na P Cl P tot P tot P tot E eqK + E eqNa + E eqCl

6. 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

7. Origin of Resting Membrane Potential

8. Contribution of Na + /K + pump  Maintenance of concentration gradients for K + and Na + across cell membranes.  Electrogenic: creates additional negativity ~4 mV.

9. Measurement of membrane potential

10. Nerve Action Potential Voltage-gated Na + channels 1.Voltage gated K + channels 2.K + leak channels 3.Na + /K + pump

11. Voltage-gated Na + and K + channels

12. Action Potential

13. Role of Ca 2+ c(Ca i )=10 -7 mol/l c(Ca o )= 10 -3 mol/l  Strong concentration gradient (10 000-fold concentration difference)  In resting state, permeability for Ca 2+ negligable. voltage-gated Ca 2+ channels  In heart cells, voltage-gated Ca 2+ channels participate in action potential (plateau).

14. Action potential with plateau (heart)

15. Initiation of action potentials depolarization  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.

16. Initiation of action potentials Acute local potentials”  “Acute local potentials” must reach threshold for eliciting AP  “all or nothing” phenomenon.

17. Refractory Period relative  Period of decreased excitability (relative r.p.) or complete inexcitability (absolute r.p.)during and after action potential. mV

18. 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.

19. Spontaneous rhythmicity  Resting membrane potential -60 do -70 mV (close to threshold)  activation Na + and Ca 2+ channels.  Depolarizationa activates slow K + channels  repolarization i hyperpolarization.

20. Propagation of action potentials

21. 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.

22. 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.