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

Nguyen HM,Miyazaki H,Hoshi N,Smith BJ,Nukina N,Goldin AL,Chandy KG

doi

10.1073/pnas.1209142109

subject

Has Abstract

pub_date

2012-11-06 00:00:00

pages

18577-82

issue

45

eissn

0027-8424

issn

1091-6490

pii

1209142109

journal_volume

109

pub_type

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