excitable membranes

1. excitablemembranes action potential & propagation Basic Neuroscience NBL 120 (2007)

2. ionic basis of APs • action potentials: • faithfully transmit information along the membrane (axon) of excitable cells • allow rapid communication between distant parts of a neuron

3. action potentials • the action potential is a regenerative electrochemical signal • two distinct voltage-gated ion channels are responsible for action potential generation

4. the action potential • 3 main stages: • resting • i.e. RMP • depolarization • reversal of membrane potential • repolarization • return of membrane potential to RMP

5. general rule ENa +67 membrane potential (mV) • relationship between: membrane potentialion equilibrium potentials • if the membrane becomes more permeable to one ion over other ions then the membrane potential will move towards the equilibrium potential for that ion (basis of AP). RMP ECl -90 EK -98

6. depolarization • rapid opening of Na-selective channels • entry of Na “down” its electrochemical gradient • 1. membrane more permeable to Na than K • 2. membrane potential moves towards Ena • 3. because ENa is +ve the AP overshoots zero • 4. At the peak of the AP Na is the primary ion determining the membrane potential

7. repolarization • closure (inactivation) of Na-selective channels • slower opening of K-selective channels • 1. membrane more permeable to K than Na • 2. membrane potential moves towards EK

8. voltage-gated ion channels • the opening and closing of AP Na and K channels are controlled by changes in the membrane potential

9. voltage-clamp • properties (e.g. time course) of voltage-gated channels are more easily examined using the voltage-clamp • holds or clamps the membrane constant • movement of ions (current) through the channels is measured directly

10. general rule ENa +67 membrane potential (mV) • relationship between: membrane potentialion equilibrium potentials • artificial manipulation of MP (voltage-clamp) - current will flow in the direction to move the MP towards the equilibrium potential of open ion channel RMP ECl -90 EK -98

11. AP current time course • voltage-clamp used to rapidly change the membrane potential over the same range as occurs during the AP • 2 current phases • rapid / transient inward current • slower outward steady current

12. the inward phase • carried by Na ions

13. 2 independent channels • selective agents block the 2 components

14. what triggers an AP? • all-or-none • AP are not graded potentials • threshold • in order for an AP to occur the membrane must be depolarized beyond a threshold level • inward Na overcomes resting outward K movement • electrical stimulation • synaptic activation

15. APs are regenerative • activation of Na channels is cyclical • initial depolarization • opening of Na channels • Na entry • etc..

16. accomodation • side-effects of inactivation • disease (e.g. paramyotonia congenita)

17. action potential review Press button

18. membrane capacitance properties • “bulk” solutions in and out are neutral • the transmembrane potential difference exists within a narrow band just across the membrane • capacitor: • separates / stores charge

19. time constant • changing the membrane voltage takes time • charging a capacitor is not instantaneous inject current V record voltage I m= rmcm axon

20. how can AP rise so fast? m= rmcm

21. how electrical signals propagate • passive decay • length constant

22. length constant (passive process) membrane resistance (rm) axon / dendrite diameter (d) axial, or internal, resistance (ri) rm ri (+ re)  =

23. AP propagation • APs are conducted along excitable cell membranes away from their point of origin • e.g. down the axon from cell soma to terminal

24. local circuits • depolarization of the membrane during the AP is not restricted to a single spot • the inward current carried by Na ions during the AP depolarizes adjacent portions of the membrane beyond threshold and the regenerative AP travels (in both directions) along the membrane

25. refractory period • following a single AP a second AP cannot be generated at the same site for some time (absolute versus relative) • Na channels need to recover from inactivation • open K channels oppose inward Na movement

26. myelination • local circuit propagation is slow (< 2 m/s) • In motorneurons propagation is fast 100 m/s • Schwann cell • envelop axons / layer of insulation • increase resistance (Rm) (increase length constant) • eliminate capacitance (time constant > 0) • Nodes of Ranvier • discontinuity in myelin sheath (every few 200+ m)

27. saltatory conduction • APs are only generated at Nodes of Ranvier • high density of Na / K channels • current flows rapidly between nodes • little current leakage between nodes • AP “jumps” down fiber as successive nodal membrane capacitances are discharged

28. propagation review Press button

29. myelination disease • Charcot-Marie tooth disease • progressive loss of PNS axons - weakness, atrophy Node of Ranvier Schwann cell

30. summary • RMP • electrochemical gradients • Nernst equation • AP initiation • role of voltage-sensitive Na and K channels • regenerative depolarization • threshold and accommodation • passive properties • time and length constants • capacitance • AP propagation • local circuits • saltatory conduction