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Biophys J, September 2000, p. 1369-1378, Vol. 79, No. 3

MinK Endows the IKs Potassium Channel Pore with Sensitivity to Internal Tetraethylammonium

Federico Sesti, Kwok-Keung Tai, and Steve A. N. Goldstein

Section of Developmental Biology and Biophysics, Departments of Pediatrics and Cellular and Molecular Physiology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536 USA

IKs channels are heteromeric complexes of pore-forming KvLQT1 subunits and pore-associated MinK subunits. Channels formed only of KvLQT1 subunits vary from IKs channels in their gating kinetics, single-channel conductance, and ion selectivity. Here we show that IKs channels are more sensitive to blockade by internal tetraethylammonium ion (TEA) than KvLQT1 channels. Inhibition by internal TEA is shown to proceed by a simple bimolecular interaction in the IKs conduction pathway. Application of a noise-variance strategy suggests that MinK enhances blockade by increasing the dwell time of TEA on its pore site from ~70 to 370 µs. Mutation of consecutive residues across the single transmembrane segment of MinK identifies positions that alter TEA blockade of IKs channels. MinK is seen to determine the pharmacology of IKs channels in addition to establishing their biophysical attributes.

Biophys J, September 2000, p. 1369-1378, Vol. 79, No. 3
© 2000 by the Biophysical Society   0006-3495/00/09/1369/10  $2.00



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