Hydrogen sulfide dilates cerebral arterioles by activating smooth muscle cell plasma membrane KATP channels

Guo Hua Liang, Adebowale Adebiyi, M. Dennis Leo, Elizabeth M. McNally, Charles W. Leffler, Jonathan H. Jaggar

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Hydrogen sulfide (H2S) is a gaseous signaling molecule that appears to contribute to the regulation of vascular tone and blood pressure. Multiple potential mechanisms of vascular regulation by H2S exist. Here, we tested the hypothesis that piglet cerebral arteriole smooth muscle cells generate ATP-sensitive K+ (KATP) currents and that H2S induces vasodilation by activating KATP currents. Gas chromatography/mass spectrometry data demonstrated that after placing Na2S, an H2S donor, in solution, it rapidly (1 min) converts to H2S. Patch-clamp electrophysiology indicated that pinacidil (a KATP channel activator), Na2S, and NaHS (another H2S donor) activated K+ currents at physiological steadystate voltage (~50 mV) in isolated cerebral arteriole smooth muscle cells. Glibenclamide, a selective KATP channel inhibitor, fully reversed pinacidil-induced K+ currents and partially reversed (~58%) H2S-induced K+ currents. Western blot analysis indicated that piglet arterioles expressed inwardly rectifying K+ 6.1 (Kir6.1) channel and sulfonylurea receptor 2B (SUR2B) KATP channel subunits. Pinacidil dilated pressurized (40 mmHg) piglet arterioles, and glibenclamide fully reversed this effect. Na2S also induced reversible and repeatable vasodilation with an EC50 of ~30 μM, and this effect was partially reversed (~55%) by glibenclamide. Vasoregulation by H2S was also studied in pressurized resistance-size cerebral arteries of mice with a genetic deletion in the gene encoding SUR2 (SUR2 null). Pinacidiland H2S-induced vasodilations were smaller in arterioles of SUR2 null mice than in wild-type controls. These data indicate that smooth muscle cell KATP currents control newborn cerebral arteriole contractility and that H2S dilates cerebral arterioles by activating smooth muscle cell KATP channels containing SUR2 subunits.

Original languageEnglish (US)
Pages (from-to)H2088-H2095
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume300
Issue number6
DOIs
StatePublished - Jun 2011

Keywords

  • Adenosine 5'-triphosphate-sensitive potassium channels
  • Arteriole smooth muscle cells
  • Sulfonylurea receptor 2

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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