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Direct Stimulation of K_ATP Channels by Exogenous and Endogenous Hydrogen Sulfide in Vascular Smooth Muscle Cells

Departments of Physiology (G.T., W.L., R.W.) and Pharmacology (L.W.), College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

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 µM 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.

Address correspondence to: Dr. Rui Wang, FAHA, Department of Physiology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada. E-mail: rwang{at}lakeheadu.ca

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