Endothelin-1 inhibition of the ATP-Sensitive K+ channel in guinea-pig ventricular cardiomyocytes

1. Effects of endothelin-1, on the ATP-sensitive K+ channel were examined in guinea-pig ventricular cardiomyocytes. 2. The ATP-sensitive K+ channel was activated outwardly with amplitude of about 2.2 pA at 0 mV. The conductance was 31 pS at 5.4 mM external K+ solution. The open probability was inhibited, and was completely blocked at 1 nM of endothelin-1. 3. In contrast, endothelin-3 (1 nM) did not cause any effects on the channels. 4. Endothelin-1 (10 nM) significantly prolonged the action potential duration. These responses were reversible. 5. These results suggest that endothelin-1 may reverse the physiological responses to the stimulation of ATP-sensitive K+ channels, indicating its regulatory mechanisms under the disease conditions.