title: Separation of P/C- and U-type inactivation pathways in Kv1.5 potassium channels.
abstract: P/C-type inactivation of Kv channels is thought to involve conformational changes in the outer pore of the channel, culminating in a partial constriction of the selectivity filter. Recent studies have identified a number of phenotypic differences in the inactivation properties of different Kv channels, including different sensitivities to elevation of extracellular K+ concentration, and different state dependencies of inactivation. We have demonstrated that an alternatively spliced short form of Kv1.5, resulting in disruption of the T1 domain, exhibits a shift in the state dependence of inactivation in this channel, and in the current study we have examined this further to contrast the properties of inactivation from open versus closed states. In a TEA+-sensitive mutant of Kv1.5 (Kv1.5 R487T), 10 mM extracellular TEA+ inhibits inactivation in both full-length and T1-deleted channels, but does not inhibit closed-state inactivation in T1-deleted channel forms. Similarly, substitution of K+ and Na+ with Cs+ ions in the recording medium inhibits inactivation of both full-length and T1-deleted channel forms, but fails to inhibit closed-state inactivation of T1-deleted channels. Collectively, these data distinguish between open-state and closed-state inactivation, and suggest the presence of multiple possible mechanisms of inactivation coexisting in Kv1 channels.
authors: Department of Cellular and Physiological Sciences, University of British Columbia, 2146 Health Sciences Mall, Vancouver B.C. V6T 1Z3, Canada.
authors: Harley T
authors: HT
authors: Kurata
authors: Kyle W
authors: KW
authors: Doerksen
authors: Jodene R
authors: JR
authors: Eldstrom
authors: Saman
authors: S
authors: Rezazadeh
authors: David
authors: D
authors: Fedida
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002586:Cesium / Q000378:metabolism; D004285:Dogs; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D007668:Kidney; D051666:Kv1.5 Potassium Channel / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D009206:Myocardium; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012413:Rubidium / Q000378:metabolism; D017384:Sequence Deletion; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D002586:Cesium; D019789:Tetraethylammonium; D012413:Rubidium; D011188:Potassium