1. Cellular Neuroscience (207) Ian Parker Lecture # 5 - Action potential propagation http://parkerlab.bio.uci.edu

2. The problem – axons are not a very good electrical wire RMRM CMCM RARA IN OUT The axoplasmic resistance R A is high (axons are a very long, thin tube), and the membrane resistance R M forms a series of potential dividers, so a voltage at one end steadily decrements along the length of the axon. AND, for fast changing signals charging of the membrane capacitance C M further causes the signal to diminish. So, injection of a square pulse of current at one end of an axon induces a passive voltage change whose amplitude declines exponentially (space constant) with distance. And, the voltage change becomes progressively more rounded as the axon membrane acts like a low-pass filter. Space constant is typically ~ 1 mm – not nearly enough to get a signal to your big toe!

3. Solution – the action potential serves as an amplifier to boost the signal as it travels along the axon. If an axon membrane is depolarized to threshold (~ -35 mV) it will trigger an all- or-none action potential, that depolarizes to ~ +50 mV Local circuits Action potential - - - - - - - - - - - - - + + + - - - - - - - - - - - - - - - Excited region of axon at instant of time Passive current flow depolarizes membrane ahead of action potential Depolarization here has no effect as membrane is refractory

4. What limits the propagation velocity of an action potential? The excited region of membrane at an action potential must depolarize the membrane ahead past threshold. This involves charging the membrane capacitance. So, back to RC circuits. membrane E (voltage at peak of action potential RARA CMCM Voltage at membrane ahead of the action potential will rise exponentially with time constant t = R A * C M (Resistance of extracellular fluid is low compared to RA, so we ignore it) Thus, an axon will transmit faster if either or both; (i)R A is smaller, (ii)C M is smaller

5. How to make a faster axon… 1. The ‘brute force & ignorance method (like a squid) Relationship between axon diameter and conduction velocity Cross section of an axon Membrane area per unit length proportional to 2 p r i.e. membrane capacitance increases linearly with radius. Cross sectional area proportional to p r 2 i.e. longitudinal axonal resistance decreases as the square of the radius Thus, the net effect is that the time constant for charging the membrane capacitance shortens about linearly with increasing radius. So, doubling the diameter of an axon will speed action potential propagation about 2x, tripling the diameter will speed about 3x and so on. The squid takes this to an extreme. But, you can’t fit many giant axons into a sciatic nerve!

6. How to make a faster axon… 2. The intelligent way – myelinating the axon to increase effective membrane thickness and thereby decrease membrane capacitance without much increasing the diameter of the axon Cross section of an unmyelinated axon Cross section of myelinated axon Overall diameter not much increased Membrane thickness many- fold increased Capacitance decreases linearly with increasing thickness of dielectric (membrane). Because a cell membrane is so thin to begin with (~ 7nm), capacitance can be reduced >50-fold with only a modest increase of diameter of the axon as a whole. Myelination achieved by oligodendrocytes wrapping themselves around and around the axon (like a Swiss roll), leaving behind double-layers of cell membrane.

7. Problem – if all the axon were myelinated, no space left to put Na channels. Solution – leave gaps of exposed axon membrane – Nodes of Ranvier Propagation of the action potential is saltatory; jumps from node to node. The delay in triggering an action potential at the next node is small (i,.e propagation speed is fast), because time constant for charging the intervening myelinated segment is fast. A safety margin is built in – passive electrotonic spread allows the action potential to skip over 2 or 3 damaged nerves before it is attenuated below threshold.