title: Modulation of voltage-gated K+ channels by the sodium channel β1 subunit.
abstract: Voltage-gated sodium (Na(V)) and potassium (K(V)) channels are critical components of neuronal action potential generation and propagation. Here, we report that Na(V)β1 encoded by SCN1b, an integral subunit of Na(V) channels, coassembles with and modulates the biophysical properties of K(V)1 and K(V)7 channels, but not K(V)3 channels, in an isoform-specific manner. Distinct domains of Na(V)β1 are involved in modulation of the different K(V) channels. Studies with channel chimeras demonstrate that Na(V)β1-mediated changes in activation kinetics and voltage dependence of activation require interaction of Na(V)β1 with the channel's voltage-sensing domain, whereas changes in inactivation and deactivation require interaction with the channel's pore domain. A molecular model based on docking studies shows Na(V)β1 lying in the crevice between the voltage-sensing and pore domains of K(V) channels, making significant contacts with the S1 and S5 segments. Cross-modulation of Na(V) and K(V) channels by Na(V)β1 may promote diversity and flexibility in the overall control of cellular excitability and signaling.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697, USA.
authors.forename: Hai M
authors.initials: HM
authors.lastname: Nguyen
authors.forename: Haruko
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Naoto
authors.initials: N
authors.lastname: Hoshi
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Smith
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nukina
authors.forename: Alan L
authors.initials: AL
authors.lastname: Goldin
authors.forename: K George
authors.initials: KG
authors.lastname: Chandy
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015640:Ion Channel Gating; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D016716:PC12 Cells; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D062547:Voltage-Gated Sodium Channel beta-1 Subunit / Q000378:metabolism*; D014981:Xenopus
chemical_list: D024642:Potassium Channels, Voltage-Gated; D062547:Voltage-Gated Sodium Channel beta-1 Subunit