Hydrogen Sulfide Opens the KATP Channel on Rat Atrial and Ventricular Myocytes

Abstract

Objective: Hydrogen sulfide (H₂S), an endogenous gaseous transmitter, was found to protect the heart from various forms of injury, but the underlying mechanism is not known. H₂S can open the K_ATP channel on vascular smooth muscle cells, and the objective of this study was to determine whether H₂S can open the K_ATP channel on myocardiocytes. Methods: The whole-cell patch-clamp technique was used to record I_K,ATP and action potentials of atrial and ventricular myocytes isolated from the hearts of male Wistar rats. Sodium hydrogen sulfide (NaHS) was used as a donor of H₂S to observe the effect of exogenous H₂S on I_K,ATP. DL-propargylglycine (PPG), an inhibitor of the synthesis of H₂S, was used at a concentration of 200 µM to observe the effect of endogenous H₂S on I_K,ATP. Results: NaHS at concentrations (in µM) of 9.375, 18.75, 37.5, 75 and 150 increased I_K,ATP by 12.8% (p > 0.05), 28.4% (p < 0.05), 38.8% (p < 0.01), 51.2% (p < 0.01) and 58.6% (p< 0.01) on ventricular myocytes, respectively, and by 6.8% (p > 0.05), 10.4% (p > 0.05), 18.9% (p < 0.01), 24.8% (p < 0.01) and 37.2% (p < 0.01) on atrial myocytes, respectively. The H₂S-induced decrease in the duration of action potentials (APD₉₀) of ventricular myocytes was concentration-dependent, although only NaHS at a concentration of 150 µM decreased the APD₉₀ significantly (15%, p < 0.05). The H₂S-induced decrease in APD₉₀ on atrial myocytes was concentration dependent, but the statistical difference was not significant. Inhibition of I_K,ATP by PPG was time dependent and the level of inhibition was: ventricular myocytes, 7% (p > 0.05), 10% (p < 0.05), 15.3% (p < 0.01), 24.0% (p < 0.01) and 28.9% (p < 0.01); atrial myocytes, 15.8% (p > 0.05), 21.3% (p > 0.05), 26.5% (p < 0.01), 34.0% (p < 0.01) and 43.2% (p < 0.01) measured at 5, 10, 15, 20 and 25 min, respectively. The increase in the APD₉₀, by PPG was time dependent for ventricular myocytes [increased by 12.8% (p < 0.05) at 25 min]. The same was true for atrial myocytes, although only the value at 25 min was significant (15%, p < 0.05). Conclusions: H₂S decreased the APD₉₀,and both the endogenous and exogenous H₂S-induced increase in I_K,ATP on both atrial and ventricular myocytes was concentration dependent. These results may help to explain, at least in part, how H₂S protects heart cells from various forms of injury.