Inactivation of voltage-gated delayed potassium current in molluscan neurons. A kinetic model

Abstract

Voltage-gated delayed potassium current in molluscan neurons is characterized by a marked inactivation. Inactivation can accumulate between repetitive pulses, giving rise to current patterns in which the maximum current during a second voltage pulse is less than the current at the end of the preceding pulse (cumulative inactivation). Other features of inactivation of this current include an onset time-course that can be characterized by the sum of two exponential processes and an early minimum in the recovery-vs.-time curve. A simple four-state model is developed that can, when supplied with rate constants derived from voltage-clamp experiments, reproduce these features of inactivation. The model incorporates state-dependent inactivation rates. Upon depolarization, both open and closed channels can be inactivated, although inactivation of closed channels is much faster. Upon repolarization, recovery from inactivated states is sufficiently slow that little recovery occurs during a short interpulse interval. Cumulative inactivation comes about as a result of fast inactivation during the second pulse, further limiting the peak current from the level at the end of the previous pulse.