This study reveals the biophysical mechanism by which the KCNE1 beta-subunit modulates the cardiac I(Ks) potassium channel, showing it requires the movement of multiple voltage sensors before channel opening.
Challenges single-sensor I(Ks) models; leaves open validation in native human cardiomyocytes.
The delayed rectifier I(Ks) potassium channel, formed by coassembly of α- (KCNQ1) and β- (KCNE1) subunits, is essential for cardiac function. Although KCNE1 is necessary to reproduce the functional properties of the native I(Ks) channel, the mechanism(s) through which KCNE1 modulates KCNQ1 is unknown. Here we report measurements of voltage sensor movements in KCNQ1 and KCNQ1/KCNE1 channels using voltage clamp fluorometry. KCNQ1 channels exhibit indistinguishable voltage dependence of fluorescence and current signals, suggesting a one-to-one relationship between voltage sensor movement and channel opening. KCNE1 coexpression dramatically separates the voltage dependence of KCNQ1/KCNE1 current and fluorescence, suggesting an imposed requirement for movements of multiple voltage sensors before KCNQ1/KCNE1 channel opening. This work provides insight into the mechanism by which KCNE1 modulates the I(Ks) channel and presents a mechanism for distinct β-subunit regulation of ion channel proteins.
No takes yet. Share an insight, caveat, or question.
Osteen et al. (2010) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: