Direct stimulation of K(ATP) 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. H2S, as a novel gasotransmitter, 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 microM 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 H2S in resistance artery VSMC, thus helping elucidate cardiovascular functions of this endogenous gas.
Tang
Guanghua
G
FAHA, Department of Physiology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada.
Wu
Lingyun
L
Liang
Wenbin
W
Wang
Rui
R
D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004594:Electrophysiology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008564:Membrane Potentials; D008638:Mesenteric Arteries; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats
D015221:Potassium Channels; D006152:Cyclic GMP; D006862:Hydrogen Sulfide