Direct stimulation of KATP channels by exogenous and endogenous hydrogen sulfide in vascular smooth muscle cells

ATP-sensitive K+ (K-ATP) channels in vascular smooth muscle cells (VSMC) are important targets for endogenous metabolic regulation and exogenous drug therapy. H 2 S, as a novel gaso-transmitter, has been shown to relax rat aortic tissues via opening of K-ATP channels. However, interaction of H2S, exogenous-applied or endogenous-produced, with K-ATP channels in resistance artery VSMC has not been delineated. In the present study, using the whole-cell and single-channel patch-clamp technique, we demonstrated that exogenous H2S activated K-ATP channels and hyperpolarized cell membrane in rat mesenteric artery VSMC. H2S enhanced the amplitude of whole-cell K-ATP currents with an EC50 value of 116 +/- 8.3 mu M and increased the open probability of single K-ATP channels. H2S hyperpolarized membrane potentials by -12 mV in nystatin-perforated VSMC. Furthermore, inhibition of endogenous H2S production with D, L-propargylglycine (PPG) reduced whole-cell K-ATP currents. PPG alone had no effect on unitary K-ATP channel currents in cell-free membrane patches. In addition, effects of H2S on K-ATP channels and membrane potentials were independent of cGMP-mediated phosphorylation. This study demonstrated modulation of K-ATP channel activity by exogenous and endogenous H 2 S in resistance artery VSMC, thus helping elucidate cardiovascular functions of this endogenous gas.