title: Altered state dependence of c-type inactivation in the long and short forms of human Kv1.5.
abstract: Evidence from both human and murine cardiomyocytes suggests that truncated isoforms of Kv1.5 can be expressed in vivo. Using whole-cell patch-clamp recordings, we have characterized the activation and inactivation properties of Kv1.5DeltaN209, a naturally occurring short form of human Kv1.5 that lacks roughly 75% of the T1 domain. When expressed in HEK 293 cells, this truncated channel exhibited a V(1/2) of -19.5 +/- 0.9 mV for activation and -35.7 +/- 0.7 mV for inactivation, compared with a V(1/2) of -11.2 +/- 0.3 mV for activation and -0.9 +/- 1.6 mV for inactivation in full-length Kv.15. Kv1.5DeltaN209 channels exhibited several features rarely observed in voltage-gated K(+) channels and absent in full-length Kv1.5, including a U-shaped voltage dependence of inactivation and "excessive cumulative inactivation," in which a train of repetitive depolarizations resulted in greater inactivation than a continuous pulse. Kv1.5DeltaN209 also exhibited a stronger voltage dependence to recovery from inactivation, with the time to half-recovery changing e-fold over 30 mV compared with 66 mV in full-length Kv1.5. During trains of human action potential voltage clamps, Kv1.5DeltaN209 showed 30-35% greater accumulated inactivation than full-length Kv1.5. These results can be explained with a model based on an allosteric model of inactivation in Kv2.1 (Klemic, K.G., C.-C. Shieh, G.E. Kirsch, and S.W. Jones. 1998. Biophys. J. 74:1779-1789) in which an absence of the NH(2) terminus results in accelerated inactivation from closed states relative to full-length Kv1.5. We suggest that differential expression of isoforms of Kv1.5 may contribute to K(+) current diversity in human heart and many other tissues.
authors.affiliation: Department of Physiology, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
authors.forename: H T
authors.initials: HT
authors.lastname: Kurata
authors.forename: G S
authors.initials: GS
authors.lastname: Soon
authors.forename: D
authors.initials: D
authors.lastname: Fedida
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002460:Cell Line; D004594:Electrophysiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007700:Kinetics; D051666:Kv1.5 Potassium Channel; D051379:Mice; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D051637:Shaker Superfamily of Potassium Channels
chemical_list: C496981:KCNA5 protein, human; C496982:Kcna5 protein, mouse; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051637:Shaker Superfamily of Potassium Channels