Involvement of the phosphatidylinositol kinase pathway in augmentation of ATP-sensitive K+ channel currents by hypo-osmotic stress in rat ventricular myocytes

The objective of this study was to investigate the mechanisms of increase in the efficacy of ATP-sensitive K+ channel (KATP) openings by hypo-osmotic stress. The whole-cell KATP currents (IK,ATP) stimulated by 100 μmol/L pinacidil, a K+ channel opening drug, were significantly augmented during hypo-osmotic stress (189 mOsmol/L) compared with normal conditions (303 mOsmol/L). The EC50 and Emax value for pinacidil-activated IK,ATP (measured at 0 mV) was 154 μmol/L and 844 pA, respectively, in normal solution and 16.6 μmol/L and 1266 pA, respectively, in hypo-osmotic solution. Augmentation of IK,ATP during hypo-osmotic stress was attenuated by wortmannin (50 μmol/L), an inhibitor of phosphatidylinositol 3- and 4-kinases, but not by (i) phalloidin (30 μmol/L), an actin filament stabilizer, (ii) the absence of Ca2+ from the internal and external solutions, and (iii) the presence of creatine phosphate (3 mmol/L), which affects creatine kinase regulation of the KATP channels. In the single-channel recordings, an...