The cardiotonic bipyridine AWD 122-60 inhibits adenosine triphosphate-sensitive potassium channels of mouse skeletal muscle.

Abstract

The inhibition of ATP-sensitive potassium channels in mouse skeletal muscle by the cardiotonic bipyridine AWD 122-60 was investigated with the patch-clamp technique. In excised patches of the inside-out configuration, internally applied AWD 122-60 (10(-6)-10(-3) mol/l) reversibly reduced the open-probability of single ATP-sensitive potassium channels. The agent shortened the periods of channel activity but did not affect the channel conductance. At positive membrane potentials channel inhibition by AWD 122-60 was more pronounced than at negative potentials, the drug concentrations producing 50% channel inhibition were 11 mumol/l at +40 mV and 29 mumol/l at -40 mV. The Hill coefficients of the concentration-response curves were in the range between 0.5 and 0.6 for both potentials. Internal application of another cardiotonic bipyridine, milrinone (10(-4) mol/l), had no effects on ATP-sensitive potassium channels in skeletal muscle. Possible effects of the inhibition of ATP-sensitive potassium channels in heart muscle by AWD 122-60 are discussed.