CLONED NEURONAL IK(A) CHANNELS REOPEN DURING RECOVERY FROM INACTIVATION

THE kinetic behaviour and functional role of potassium ion (K+) channels mediating a fast-inactivating K+ current (I(K)(A)) has been widely discussed 1. Activating in the subthreshold range of excitation, I(K)(A) channels are assumed to reduce the excitatory effect of depolarizing membrane currents in a time-dependent manner. Here we report that I(K)(A) channels not only open in response to a depolarization but open again after repolarization of the membrane. Although the current in response to the depolarization is rapidly inactivating, the current elicited by repolarization declines slowly and produces long-lasting after hyperpolarizations under current-clamp conditions. This implies an additional physiological role for I(K)(A) channels, particularly those that activate positive to the threshold of excitation. The underlying biophysical mechanism was studied by fast-application of peptides corresponding to the N-terminal end of the I(K)(A) channel proteins. It was found to be a voltage-dependent release of the inactivation gate.