Modulation of voltage-gated K⁺ channels by the sodium channel β1 subunit

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 Vβ1 encoded by SCN1b , an integral subunit of Na V channels, coassembles with and modulates the biophysical properties of K V1 and K V7 ch...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2012-11, Vol.109 (45), p.18577-18582
Main Authors: Nguyen, Hai M, Miyazaki, Haruko, Hoshi, Naoto, Smith, Brian J, Nukina, Nobuyuki, Goldin, Alan L, Chandy, K. George
Format: Article
Language:English
Subjects:
Action potentials
Animals
Axons
Biological Sciences
Chimeras
chimerism
CHO Cells
Cricetinae
Cricetulus
Electric potential
Epilepsy
Ion Channel Gating
Ion channels
Kinetics
Mice
Models, Molecular
Molecular interactions
Oocytes
PC12 Cells
potassium
potassium channels
Potassium Channels, Voltage-Gated - chemistry
Potassium Channels, Voltage-Gated - metabolism
Protein Binding
Protein Structure, Tertiary
Rats
sodium
Sodium channels
Voltage-Gated Sodium Channel beta-1 Subunit - metabolism
Xenopus
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 Vβ1 encoded by SCN1b , an integral subunit of Na V channels, coassembles with and modulates the biophysical properties of K V1 and K V7 channels, but not K V3 channels, in an isoform-specific manner. Distinct domains of Na Vβ1 are involved in modulation of the different K V channels. Studies with channel chimeras demonstrate that Na Vβ1-mediated changes in activation kinetics and voltage dependence of activation require interaction of Na Vβ1 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 Vβ1 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 Vβ1 may promote diversity and flexibility in the overall control of cellular excitability and signaling.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1209142109