A voltage-dependent role for K+ in recovery from C-type inactivation.
Recovery from C-type inactivation of Kv1.3 can be accelerated by the binding of extracellular potassium to the channel in a voltage-dependent fashion. Whole-cell patch-clamp recordings of human T lymphocytes show that Ko+ can bind to open or inactivated channels. Recovery is biphasic with time constants that depend on the holding potential. Recovery is also dependent on the voltage of the depolarizing pulse that induces the inactivation, consistent with a modulatory binding site for K+ located at an effective membrane electrical field distance of 30%. This K(+)-enhanced recovery can be further potentiated by the binding of extracellular tetraethylammonium to the inactivated channel, although the tetraethylammonium does not interact directly with the K(+)-binding site. Our findings are consistent with a model in which K+ can bind and unbind slowly from a channel in the inactivated state, and inactivated channels that are bound by K+ will recover with a rate that is fast relative to unbound channels. Our data suggest that the kinetics of K+ binding to the modulatory site are slower than these recovery rates, especially at hyperpolarized voltages.
Levy
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Department of Physiology, University of Pennsylvania, Philadelphia 19104-6085, USA.
Deutsch
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C
D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051664:Kv1.3 Potassium Channel; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D013601:T-Lymphocytes / Q000502:physiology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
C496973:KCNA3 protein, human; D051664:Kv1.3 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D011188:Potassium