Mechanism and modulation of inactivation of the Kv3 potassium channel

The mechanism and modulation of inactivation of the rat brain voltage-gated potassium channel, Kv3, expressed in Xenopus oocytes, were examined. In the cell-attached patch recording mode, Kv3 macroscopic current amplitude remains constant from one pulse to the next when a series of short (15 ms) repetitive depolarizing pulses are given. However, when the membrane patch is detached from the cell, the current amplitude decreases substantially from one depolarizing pulse to the next, even though there is no significant inactivation-like behaviour within a single current trace. In contrast, the closely related Kv2 potassium channel does not show a similar modulation of inactivation on changing from the cell-attached to the detached-patch recording mode. The data indicate the existence of a prolonged non-conducting state which the Kv3 channel enters in response to a series of short depolarizing pulses; this state is identical to the C-type inactivation state into which channels are driven during individual long depolarizing pulses. The probability of finding the channel in this state differs between the cell-attached and detached-patch modes, indicating that it is modulated by some cytoplasmic factor.