Regulation of Voltage-Activated K+ Channel Gating by Transmembrane β Subunits

Xiaohui Sun,Jianmin Cui,Mark A Zaydman

doi:10.3389/fphar.2012.00063

Abstract

Voltage-activated K+ (KV) channels are important for shaping action potentials and maintaining resting membrane potential in excitable cells. KV channels contain a central pore-gate domain (PGD) surrounded by four voltage-sensing domains (VSDs). The VSDs will change conformation in response to alterations of the membrane potential thereby inducing the opening of the PGD. Many KV channels are heteromeric protein complexes containing auxiliary β subunits. These β subunits modulate channel expression and activity to increase functional diversity and render tissue specific phenotypes. This review focuses on the KV β subunits that contain transmembrane (TM) segments including the KCNE family and the β subunits of large conductance, Ca2+- and voltage-activated K+ (BK) channels. These TM β subunits affect the voltage-dependent activation of KV α subunits. Experimental and computational studies have described the structural location of these β subunits in the channel complexes and the biophysical effects on VSD activation, PGD opening, and VSD–PGD coupling. These results reveal some common characteristics and mechanistic insights into KV channel modulation by TM β subunits.

Highlights

Cellular electrical signals organize and control activity in the nervous, muscular, and hormonal tissues
KV channels share a common topology of six TM α helices (S1–S6) that are organized into two structural domains, the voltage-sensing domain (VSD, S1–S4) and the pore-gate domain (PGD, S5 and S6)
KCNE1 participates in a broad set of interactions with KCNQ1 that span the entire length of the KCNE1 peptide. This interface includes interactions with both the VSD and the PGD, and contacts are made with as many as three KCNQ1 subunits of the tetramer. These structural models do not identify the likely mechanism for how KCNE1 modulates the voltage-dependent activation of KCNQ1 as the interactions with the VSD, PGD, and S4/S5 linker suggest that regulation of VSD movement, PGD opening, and electromechanical coupling are all plausible

Summary

Introduction

Cellular electrical signals organize and control activity in the nervous, muscular, and hormonal tissues. These structural models do not identify the likely mechanism for how KCNE1 modulates the voltage-dependent activation of KCNQ1 as the interactions with the VSD, PGD, and S4/S5 linker suggest that regulation of VSD movement, PGD opening, and electromechanical coupling are all plausible.

Results

Conclusion