The cardiotonic bipyridine AWD 122-60 inhibits adenosine triphosphate-sensitive potassium channels of mouse skeletal muscle.
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.
Bodewei
R
R
Physiologisches Institut, Universität des Saarlandes, Homburg/Saar, Federal Republic of Germany.
Hehl
S
S
Neumcke
B
B
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D020105:Milrinone; D009132:Muscles / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology
D002316:Cardiotonic Agents; D009570:Nitriles; D015221:Potassium Channels; D011725:Pyridines; D011728:Pyridones; C075268:AWD 122-60; D000255:Adenosine Triphosphate; D020105:Milrinone