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