Excitability of the squid giant axon revisited.

The electrical properties of the giant axon from the common squid Loligo pealei have been reexamined. The primary motivation for this work was the observation that the refractoriness of the axon was significantly greater than the predictions of the standard model of nerve excitability. In particular, the axon fired only once in response to a sustained, suprathreshold stimulus. Similarly, only a single action potential was observed in response to the first pulse of a train of 1-ms duration current pulses, when the pulses were separated in time by approximately 10 ms. The axon was refractory to all subsequent pulses in the train. The underlying mechanisms for these results concern both the sodium and potassium ion currents INa and IK. Specifically, Na+ channel activation has long been known to be coupled to inactivation during a depolarizing voltage-clamp step. This feature appears to be required to simulate the pulse train results in a revised model of nerve excitability. Moreover, the activation curve for IK has a significantly steeper voltage dependence, especially near its threshold (approximately -60 mV), than in the standard model, which contributes to reduced excitability, and the fully activated current-voltage relation for IK has a nonlinear, rather than a linear, dependence on driving force. An additional aspect of the revised model is accumulation/depeletion of K+ in the space between the axon and the glial cells surrounding the axon, which is significant even during a single action potential and which can account for the 15-20 mV difference between the potassium equilibrium potential EK and the maximum afterhyperpolarization of the action potential. The modifications in IK can also account for the shape of voltage changes near the foot of the action potential.