Modulation of the delayed rectifier K+ current by apamin in guinea-pig heart.

Modulation of the cardiac delayed rectifier K+ current (IK) 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 Ca(2+)-activated K+ channel activity. Bath application of apamin prolonged the action potential duration and partially inhibited IK in a concentration-dependent fashion with a half-maximal concentration of 34.4 nM and a Hill coefficient of 1.2. The inhibition of IK occurred at all voltages tested and the block was irreversible. In contrast, the activation curve (P infinity curve) of IK was not shifted by application of apamin, suggesting that the voltage dependence of IK activation is unaffected by apamin. Thus, apamin can partially inhibit cardiac IK without affecting the activation kinetics. This differential sensitivity of IK to apamin suggests that cardiac IK can be separated into two distinct channel populations: the apamin-sensitive K+ channels and the apamin-insensitive K+ channels.