Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a K+ channel.
Quaternary ammonium blockers inhibit many voltage-activated potassium (K+) channels from the intracellular side. When applied to Drosophila Shaker potassium channels expressed in mammalian cells, these rapidly reversible blockers produced use-dependent inhibition through an unusual mechanism--they promoted an intrinsic conformational change known as C-type inactivation, from which recovery is slow. The blockers did so by cutting off potassium ion flow to a site in the pore, which then emptied at a rate of 10(5) ions per second. This slow rate probably reflected the departure of the last ion from the multi-ion pore: Permeation of ions (at 10(7) per second) occurs rapidly because of ion-ion repulsion, but the last ion to leave would experience no such repulsion.
Baukrowitz
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Department of Neurobiology, Harvard Medical School and Massachusetts General Hospital, Boston 02114, USA.
Yellen
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D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D008012:Lidocaine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism / Q000494:pharmacology*; D051637:Shaker Superfamily of Potassium Channels; D013757:Tetraethylammonium Compounds / Q000378:metabolism / Q000494:pharmacology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; D051637:Shaker Superfamily of Potassium Channels; D013757:Tetraethylammonium Compounds; C012647:QX-314; D008012:Lidocaine; D011188:Potassium