Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms.
Voltage-activated K+ currents and their inactivation properties are important for controlling frequency-dependent signaling in neurons and other excitable cells. Two distinct molecular mechanisms for K+ channel inactivation have been described: N-type, which involves rapid occlusion of the open channel by an intracellular tethered blocker, and C-type, which involves a slower change at the extracellular mouth of the pore. We find that frequency-dependent cumulative inactivation of Shaker channels is very sensitive to changes of extracellular [K+] in the physiological range, with much more inactivation at low [K+]out, and that it results from the interaction of N- and C-type inactivation. N-type inactivation enhances C-type inactivation by two mechanisms. First, it inhibits outward K+ flux, which normally fills an external ion site and thus prevents C-type inactivation. Second, it keeps the channel's activation gate open even after repolarization, allowing C-type inactivation to occur for a prolonged period.
Baukrowitz
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Department of Neurobiology, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA.
Yellen
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D002460:Cell Line; D004553:Electric Conductivity; D004622:Embryo, Mammalian; D017353:Gene Deletion; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D007668:Kidney; D007700:Kinetics; D009154:Mutation; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D015221:Potassium Channels; D011188:Potassium