Interrelation between pinacidil and intracellular ATP concentrations on activation of the ATP-sensitive K+ current in guinea pig ventricular myocytes.
The patch-clamp technique was used to study the relation between pinacidil and intracellular ATP concentration [( ATP]i) on the activation of the outward K+ current in guinea pig ventricular myocytes. Pinacidil shortened the action potential duration, exhibiting stronger effect at 2 mM [ATP]i than at 5 mM [ATP]i. Pinacidil at 5 microM or higher concentrations activated the time-independent outward current at potentials positive to -80 mV, and the pinacidil-activated current was suppressed by increasing [ATP]i from 2 to 5 mM. The dose-response curve of pinacidil at different [ATP]i showed a shift to the right and a depression of the maximum response at increased [ATP]i. The pinacidil-induced shortening of the action potential duration and outward current were inhibited by application of 0.3-1.0 microM glibenclamide. In single-channel current recordings, pinacidil activated the intracellular ATP-sensitive K+ channel current without changing the unitary amplitude, and increased open probability of the channel, an effect dependent on [ATP]i. The pinacidil-activated single-channel current was blocked by glibenclamide. These results prove the notion that pinacidil activates the ATP-sensitive K+ channel current, which explains the action potential shortening in cardiac cells after application of pinacidil.
Nakayama
K
K
Department of Cardiovascular Diseases Medical Research Institute, Tokyo Medical and Dental University, Japan.
Fan
Z
Z
Marumo
F
F
Hiraoka
M
M
D000200:Action Potentials; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles; D066298:In Vitro Techniques; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D020110:Pinacidil; D011188:Potassium / Q000378:metabolism / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D006146:Guanidines; D014665:Vasodilator Agents; D020110:Pinacidil; D000255:Adenosine Triphosphate; D011188:Potassium