Abstract
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.
- Received July 29, 2005.
- Accepted September 8, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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