Hydrogen sulfide activates Ca²⁺ sparks to induce cerebral arteriole dilatation

J Physiol. 2012 Jun 1;590(11):2709-20. doi: 10.1113/jphysiol.2011.225128. Epub 2012 Apr 16.


Hydrogen sulfide (H₂S) is a gaseous vasodilator produced by endothelial cells. Mechanisms by which H₂S induces vasodilatation are unclear. We tested the hypothesis that H₂S dilates cerebral arterioles by modulating local and global intracellular Ca²⁺ signals in smooth muscle cells. High-speed confocal imaging revealed that Na₂S, an H₂S donor, increased Ca²⁺ spark frequency ∼1.43-fold and decreased global intracellular Ca²⁺ concentration ([Ca²⁺]i) by ∼37 nM in smooth muscle cells of intact piglet cerebral arterioles. In contrast, H₂S did not alter Ca²⁺ wave frequency. In voltage-clamped (-40 mV) cells, H₂S increased the frequency of iberiotoxin-sensitive, Ca²⁺ spark-induced transient Ca²⁺-activated K⁺ (KCa) currents ∼1.83-fold, but did not alter the amplitude of these events. H₂S did not alter the activity of single KCa channels recorded in the absence of Ca²⁺ sparks in arteriole smooth muscle cells. H₂S increased SR Ca²⁺ load ([Ca²⁺]SR), measured as caffeine (10 and 20mM)-induced [Ca²⁺]i transients, ∼1.5-fold. H₂S hyperpolarized (by ∼18 mV) and dilated pressurized (40 mmHg) cerebral arterioles. Iberiotoxin, a KCa channel blocker, reduced H₂S-induced hyperpolarization by ∼51%. Iberiotoxin and ryanodine, a ryanodine receptor channel inhibitor, reduced H₂S-induced vasodilatation by ∼38 and ∼37%, respectively. In summary, our data indicate that H₂S elevates [Ca²⁺]SR, leading to Ca²⁺ spark activation in cerebral arteriole smooth muscle cells. The subsequent elevation in transient KCa current frequency leads to membrane hyperpolarization, a reduction in global [Ca²⁺]i and vasodilatation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arterioles / drug effects
  • Arterioles / physiology
  • Brain / blood supply*
  • Brain / drug effects
  • Brain / physiology
  • Calcium / physiology*
  • Hydrogen Sulfide / pharmacology*
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / physiology
  • Potassium Channels, Calcium-Activated / physiology
  • Ryanodine Receptor Calcium Release Channel / physiology
  • Sarcoplasmic Reticulum / physiology
  • Swine
  • Vasodilation / drug effects*


  • Potassium Channels, Calcium-Activated
  • Ryanodine Receptor Calcium Release Channel
  • Calcium
  • Hydrogen Sulfide