Modulation of voltage-gated K+ channels by the sodium channel ß1 subunit.
Proc Natl Acad Sci U S A
; 109(45): 18577-82, 2012 Nov 06.
Article
em En
| MEDLINE
| ID: mdl-23090990
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)ß1 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)ß1 are involved in modulation of the different K(V) channels. Studies with channel chimeras demonstrate that Na(V)ß1-mediated changes in activation kinetics and voltage dependence of activation require interaction of Na(V)ß1 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)ß1 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)ß1 may promote diversity and flexibility in the overall control of cellular excitability and signaling.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Canais de Potássio de Abertura Dependente da Tensão da Membrana
/
Subunidade beta-1 do Canal de Sódio Disparado por Voltagem
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos