A HUMAN INTERMEDIATE CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNEL

An intermediate conductance calcium-activated potassium channel, hIK1, was cloned from human pancreas. The predicted amino acid sequence is related to, but distinct from, the small conductance calcium-activated potassium channel subfamily, which is approximate to 50% conserved. h IK1 mRNA was detected in peripheral tissues but not in brain. Expressi on of hIK1 in Xenopus oocytes gave rise to inwardly rectifying potassi um currents, which were activated by submicromolar concentrations of i ntracellular calcium (K-0.5 = 0.3 mu M). Although the K-0.5 for calciu m was similar to that of small conductance calcium-activated potassium channels, the slope factor derived from the Hill equation was signifi cantly reduced (1.7 vs. 3.5). Single-channel current amplitudes reflec ted the macroscopic inward rectification and revealed a conductance le vel of 39 pS in the inward direction. hIK1 currents were reversibly bl ocked by charybdotoxin (K-i = 2.5 nM) and clotrimazole (K-i = 24.8 nM) but were minimally affected by apamin (100 nM), iberiotoxin (50 nM), or ketoconazole (10 mu M). These biophysical and pharmacological prope rties are consistent with native intermediate conductance calcium-acti vated potassium channels, including the erythrocyte Gardos channel.