Interrelation Between Pinacidil and Intracellular ATP Concentrations

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 ,M 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]j. The pinacidil-induced shortening of the action potential duration and outward current were inhibited by application of 0.3-1.0 JpM 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 ATPsensitive K' channel current, which explains the action potential shortening in cardiac cells after application of pinacidil. (Circulation Research 1990;67:1124-1133)