MODULATION OF THE DELAYED RECTIFIER K+ CURRENT BY APAMIN IN GUINEA-PIG HEART

Modulation of the cardiac delayed rectifier K+ current (I-K) by apamin was studied in guinea-pig ventricular myocytes using the whole-cell configuration of the patch-clamp technique. Apamin, a peptide toxin isolated from bee venom, is known to inhibit Ca2+-activated K+ channel activity. Bath application of apamin prolonged the action potential duration and partially inhibited I-K in a concentration-dependent fashion with a half-maximal concentration of 34.4 nM and a Hill coefficient of 1.2. The inhibition of I-K occurred at all voltages tested and the block was irreversible. In contrast, the activation curve (P-infinity curve) of I-K was not shifted by application of apamin, suggesting that the voltage dependence of I-K activation is unaffected by apamin. Thus, apamin can partially inhibit cardiac I-K without affecting the activation kinetics. This differential sensitivity of I-K to apamin suggests that cardiac I-K can be separated into two distinct channel populations: the apamin-sensitive K+ channels and the apamin-insensitive K+ channels.