Voltage-dependent inactivation of the human K+ channel KvLQT1 is eliminated by association with minimal K+ channel (minK) subunits.
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 (tau = 130 +/- 10 ms), and developed after a delay of approximately 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.
Tristani-Firouzi
M
M
Department of Pediatrics, Division of Cardiology, Eccles Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112, USA.
Sanguinetti
M C
MC
D000818:Animals; D004553:Electric Conductivity; D004594:Electrophysiology; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D013997:Time Factors; D014982:Xenopus laevis
D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated