Interrelation between pinacidil and intracellular ATP concentrations on activation of the ATP-sensitive K+ current in guinea pig ventricular myocytes

Abstract

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). Pinacidil at 5 μM 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 μM 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.