Voltage‐dependent inactivation of the human K+ channel KvLQT1 is eliminated by association with minimal K+ channel (minK) subunits

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Abstract
1 The time course and voltage dependence of inactivation of KvLQT1 channels expressed in Xenopus oocytes were studied using two-microelectrode voltage-clamp techniques. 2 Tail current analysis was used to characterize the kinetics of channel inactivation and deactivation. The time constant for recovery from channel inactivation was voltage dependent and varied from 30 ± 2 ms at −90 mV to 36 ± 1 ms at −30 mV. The time constant for deactivation varied from 186 ± 21 to 986 ± 43 ms over the same voltage range. 3 Inactivation of KvLQT1 channels was incomplete, reducing fully activated current by 35 % at +40 mV. Inactivation of KvLQT1 channels was half-maximal at −18 ± 2 mV. 4 The onset of KvLQT1 channel inactivation during a single depolarization to +20 mV was exponential (τ= 130 ± 10 ms), and developed after a delay of ≈75 ms. In contrast, when inactivation was reinduced following transient recovery of channels to the open state(s), the onset of inactivation was immediate and 10 times faster. These findings suggest multiple open states, and a sequential gating model for KvLQT1 channel activation and inactivation (C1⇌ Cn⇌ O1⇌ O2⇌ I). 5 Delayed rectifier K+ (IKs) channels formed by heteromultimeric coassembly of KvLQT1 and minimal K+ channel (minK) subunits did not inactivate. Thus, minK subunits eliminate, or greatly slow, the gating associated with channel inactivation when coassembled with KvLQT1.