title: Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels.
abstract: Voltage-activated K+ channels are a family of closely related membrane proteins that differ in their gating behavior, conductance, and pharmacology. A prominent and physiologically important difference among K+ channels is their rate of inactivation. Inactivation rates range from milliseconds to seconds, and K+ channels with different inactivation properties have very different effects on signal integration and repetitive firing properties of neurons. The cloned Shaker B (H4) potassium channel is an example of a K+ channel that inactivates in a few milliseconds. Recent experiments have shown that removal of an N-terminal region of the Shaker protein by site-directed deletion practically abolishes this fast inactivation, but the modified channel does still inactivate during a prolonged depolarization lasting many seconds. Here we report that this remnant inactivation must occur by a distinct mechanism from the rapid inactivation of the wild-type Shaker channel. Like the inactivation of another K+ channel [Grissmer, S. & Calahan, M. (1989) Biophys. J. 55, 203-206], this slow inactivation is retarded by the application of a channel blocker, tetraethylammonium, to the extracellular side of the channel. By contrast, the fast inactivation of the wild-type Shaker channel is sensitive only to intracellular application of tetraethylammonium. Intracellular tetraethylammonium slows down the fast inactivation process, as though it competes with the binding of the inactivation particle.
authors.affiliation: Howard Hughes Medical Institute, Baltimore, MD 21205.
authors.forename: K L
authors.initials: KL
authors.lastname: Choi
authors.forename: R W
authors.initials: RW
authors.lastname: Aldrich
authors.forename: G
authors.initials: G
authors.lastname: Yellen
mesh_terms: D002460:Cell Line; D004247:DNA / Q000235:genetics; D006801:Humans; D015640:Ion Channel Gating; D010957:Plasmids; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*; D014162:Transfection
chemical_list: D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D004247:DNA