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

AbstractIKs 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 370μs. 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