MinK endows the I-Ks potassium channel pore with sensitivity to internal tetraethylammonium

I-Ks channels are heteromeric complexes of pore-forming KvLQT1 subunits and pore-associated MinK subunits. Channels formed only of KvLQT1 subunits var y from I-Ks channels in their gating kinetics, single-channel conductance, and ion selectivity. Here we show that I-Ks channels are more sensitive to blockade by internal tetraethylammonium ion (TEA) than KvLQT1 channels. inh ibition by internal TEA is shown to proceed by a simple bimolecular interac tion in the I-Ks conduction pathway. Application of a noise-variance strate gy suggests that MinK enhances blockade by increasing the dwell time of TEA on its pore site from similar to 70 to 370 mu s. Mutation of consecutive r esidues across the single transmembrane segment of MinK identifies position s that alter TEA blockade of I-Ks channels. MinK is seen to determine the p harmacology of I-Ks channels in addition to establishing their biophysical attributes.