MODELING STATE-DEPENDENT INACTIVATION OF MEMBRANE CURRENTS

Inactivation of many ion channels occurs through largely voltage-indep endent transitions to an inactivated state from the open state or from other states in the pathway leading to opening of the channel. Becaus e this form of inactivation is state-dependent rather than voltage-dep endent, it cannot be described by the standard Hodgkin-Huxley formalis m used in virtually all modeling studies of neuronal behavior. Using t wo examples, cumulative inactivation of the Kv3 potassium channel and inactivation of the fast sodium channel, we extend the standard formal ism for modeling macroscopic membrane currents to account for state-de pendent inactivation. Our results provide an accurate description of c umulative inactivation of the Kv3 channel, new insight into inactivati on of the sodium channel, and a general framework for modeling macrosc opic currents when state-dependent processes are involved. In a model neuron, the macroscopic Kv3 current produces a novel short-term memory effect and firing delays similar to those seen in hippocampal neurons .