The delayed rectifier IKs potassium channel, formed by co-assembly of alpha (KCNQ1) and beta (KCNE1) subunits, is essential for cardiac function. Though KCNE1 is necessary to reproduce the functional properties of the native IKs 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 expressed in Xenopus oocytes 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 co-expression dramatically separates the voltage dependence of KCNQ1/KCNE1 current and fluorescence, suggesting an imposed requirement for movements of multiple voltage sensors prior to KCNQ1/KCNE1 channel opening. This work provides the first insight into the mechanism by which KCNE1 modulates the IKs channel and presents a novel mechanism for beta subunit regulation of ion channel proteins.
University of Oxford (2011) Proc Physiol Soc 23, SA43
Research Symposium: Voltage sensor movements in cardiac IKs channels suggest a mechanism for how KCNE1 affects KCNQ1 channels
P. Larsson1, J. Osteen2, C. Gonzalez3, K. Sampson2, V. Iyer2, S. Rebolledo1, R. Kass2
1. Department of Physiology and Biophysics, University of Miami, Miami, United Kingdom. 2. Department of Pharmacology, Columbia University, New York, New York, United States. 3. Centro de Neurociencia, Universidad de Valparaiso, Valparaiso, Chile.
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