RT Journal Article SR Electronic T1 Direct Stimulation of KATP Channels by Exogenous and Endogenous Hydrogen Sulfide in Vascular Smooth Muscle Cells JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1757 OP 1764 DO 10.1124/mol.105.017467 VO 68 IS 6 A1 Guanghua Tang A1 Lingyun Wu A1 Wenbin Liang A1 Rui Wang YR 2005 UL http://molpharm.aspetjournals.org/content/68/6/1757.abstract AB ATP-sensitive K+ (KATP) channels in vascular smooth muscle cells (VSMC) are important targets for endogenous metabolic regulation and exogenous drug therapy. H2S, as a novel gasotransmitter, has been shown to relax rat aortic tissues via opening of KATP channels. However, interaction of H2S, exogenous-applied or endogenous-produced, with KATP 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 KATP channels and hyperpolarized cell membrane in rat mesenteric artery VSMC. H2S enhanced the amplitude of whole-cell KATP currents with an EC50 value of 116 ± 8.3 μM and increased the open probability of single KATP 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 KATP currents. PPG alone had no effect on unitary KATP channel currents in cell-free membrane patches. In addition, effects of H2S on KATP channels and membrane potentials were independent of cGMP-mediated phosphorylation. This study demonstrated modulation of KATP channel activity by exogenous and endogenous H2S in resistance artery VSMC, thus helping elucidate cardiovascular functions of this endogenous gas.