Key result
Single-molecule spectroscopy demonstrated that surface IKs channels with human subunits contain exactly two KCNE1 and four KCNQ1 subunits, a stoichiometry that does not vary.
Advances IKs structural models for researchers; leaves open any clinical translation to arrhythmia care.
KCNE1 (E1) β-subunits assemble with KCNQ1 (Q1) voltage-gated K(+) channel α-subunits to form IKslow (IKs) channels in the heart and ear. The number of E1 subunits in IKs channels has been an issue of ongoing debate. Here, we use single-molecule spectroscopy to demonstrate that surface IKs channels with human subunits contain two E1 and four Q1 subunits. This stoichiometry does not vary. Thus, IKs channels in cells with elevated levels of E1 carry no more than two E1 subunits. Cells with low levels of E1 produce IKs channels with two E1 subunits and Q1 channels with no E1 subunits--channels with one E1 do not appear to form or are restricted from surface expression. The plethora of models of cardiac function, transgenic animals, and drug screens based on variable E1 stoichiometry do not reflect physiology.
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Plant et al. (2014) studied this question. Single-molecule spectroscopy demonstrated that surface IKs channels with human subunits contain exactly two KCNE1 and four KCNQ1 subunits, a stoichiometry that does not vary.
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