Received for publication August 1, 2005.
Revised September 7, 2005.
Accepted for publication September 8, 2005.

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

Abstract

ATP-sensitive K⁺ (K_ATP) channels in vascular smooth muscle cells (VSMC) are important targets for endogenous metabolic regulation and exogenous drug therapy. Hydrogen sulfide (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 have 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 EC₅₀ of 116±8.3 µM and increased 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 L-propargylglycine (PPG) 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.

Key words: Ion channel regulation, Potassium, cGMP, Protein Kinase G, Regulation - physiological, Gases/general anesthetics

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