Modulation of voltage-gated K+ channels by the sodium channel beta 1 subunit

作者：Nguyen Hai M; Miyazaki Haruko; Hoshi Naoto; Smith Brian J; Nukina Nobuyuki; Goldin Alan L; Chandy K George^*

来源：Proceedings of the National Academy of Sciences, 2012, 109(45): 18577-18582.

DOI：10.1073/pnas.1209142109

• colocalization
• gating
• voltage-gated ion channels
• patch-clamp
• accessory 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-V beta 1 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 beta 1 are involved in modulation of the different K-V channels. Studies with channel chimeras demonstrate that Na-V beta 1-mediated changes in activation kinetics and voltage dependence of activation require interaction of Na-V beta 1 with the channel%26apos;s voltage-sensing domain, whereas changes in inactivation and deactivation require interaction with the channel%26apos;s pore domain. A molecular model based on docking studies shows Na-V beta 1 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 beta 1 may promote diversity and flexibility in the overall control of cellular excitability and signaling.

• 出版日期2012-11-6