EVIDENCE FOR MULTIPLE OPEN AND INACTIVATED STATES OF THE HKV1.5 DELAYED RECTIFIER

The kinetic properties cf hKv1.5, a Shaker-related cardiac delayed rec tifier. expressed in Ltk(-) cells were studied. hKv1.5 currents elicit ed by membrane depolarizations exhibited a delay followed by biphasic activation. The biphasic activation remained after 5-s prepulses to me mbrane potentials between -80 and -30 mV; however, the relative amplit ude of the slow component increased as the prepulse potential approach ed the threshold of channel activation. suggesting that the second com ponent did not reflect activation from a hesitant state. The decay of tail currents at potentials between -80 and -30 mV was adequately desc ribed with a biexponential. Th, time course of deactivation slowed as the duration of the depolarizing pulse increased. This was due to a re lative increase in the slowly decaying component, despite similar init ial amplitudes reflecting a similar open probability after 50- and 500 -ms prepulses To further investigate transitions after the initial act ivated state, we examined the temperature dependence of inactivation T he time constants of slow inactivation displayed little temperature an d voltage dependence, but the degree of the inactivation increased sub stantially with increased temperature Recovery from inactivation proce eded with a biexponential time course, but long prepulses at depolariz ed potentials slowed the apparent rate of recovery from inactivation. These data strongly indicate that hKv1.5 has both multiple open states and multiple inactivated states.