Hydrogen sulfide activates Ca 2+ sparks to induce cerebral arteriole dilatation

Guo Hua Liang, Qi Xi, Charles Leffler, Jonathan Jaggar

Research output: Contribution to journalArticle

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Abstract

Hydrogen sulfide (H 2 S) is a gaseous vasodilator produced by endothelial cells. Mechanisms by which H 2 S induces vasodilatation are unclear. We tested the hypothesis that H 2 S dilates cerebral arterioles by modulating local and global intracellular Ca 2+ signals in smooth muscle cells. High-speed confocal imaging revealed that Na 2 S, an H 2 S donor, increased Ca 2+ spark frequency ∼1.43-fold and decreased global intracellular Ca 2+ concentration ([Ca 2+ ] i ) by ∼37 nm in smooth muscle cells of intact piglet cerebral arterioles. In contrast, H 2 S did not alter Ca 2+ wave frequency. In voltage-clamped (-40 mV) cells, H 2 S increased the frequency of iberiotoxin-sensitive, Ca 2+ spark-induced transient Ca 2+ -activated K + (K Ca ) currents ∼1.83-fold, but did not alter the amplitude of these events. H 2 S did not alter the activity of single K Ca channels recorded in the absence of Ca 2+ sparks in arteriole smooth muscle cells. H 2 S increased SR Ca 2+ load ([Ca 2+ ] SR ), measured as caffeine (10 and 20 mm)-induced [Ca 2+ ] i transients, ∼1.5-fold. H 2 S hyperpolarized (by ∼18 mV) and dilated pressurized (40 mmHg) cerebral arterioles. Iberiotoxin, a K Ca channel blocker, reduced H 2 S-induced hyperpolarization by ∼51%. Iberiotoxin and ryanodine, a ryanodine receptor channel inhibitor, reduced H 2 S-induced vasodilatation by ∼38 and ∼37%, respectively. In summary, our data indicate that H 2 S elevates [Ca 2+ ] SR , leading to Ca 2+ spark activation in cerebral arteriole smooth muscle cells. The subsequent elevation in transient K Ca current frequency leads to membrane hyperpolarization, a reduction in global [Ca 2+ ] i and vasodilatation.

Original languageEnglish (US)
Pages (from-to)2709-2720
Number of pages12
JournalJournal of Physiology
Volume590
Issue number11
DOIs
StatePublished - Jun 1 2012

Fingerprint

Hydrogen Sulfide
Arterioles
Dilatation
Smooth Muscle Myocytes
Vasodilation
Ryanodine
Ryanodine Receptor Calcium Release Channel
Caffeine
Vasodilator Agents
Endothelial Cells
Membranes
iberiotoxin

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Hydrogen sulfide activates Ca 2+ sparks to induce cerebral arteriole dilatation . / Liang, Guo Hua; Xi, Qi; Leffler, Charles; Jaggar, Jonathan.

In: Journal of Physiology, Vol. 590, No. 11, 01.06.2012, p. 2709-2720.

Research output: Contribution to journalArticle

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abstract = "Hydrogen sulfide (H 2 S) is a gaseous vasodilator produced by endothelial cells. Mechanisms by which H 2 S induces vasodilatation are unclear. We tested the hypothesis that H 2 S dilates cerebral arterioles by modulating local and global intracellular Ca 2+ signals in smooth muscle cells. High-speed confocal imaging revealed that Na 2 S, an H 2 S donor, increased Ca 2+ spark frequency ∼1.43-fold and decreased global intracellular Ca 2+ concentration ([Ca 2+ ] i ) by ∼37 nm in smooth muscle cells of intact piglet cerebral arterioles. In contrast, H 2 S did not alter Ca 2+ wave frequency. In voltage-clamped (-40 mV) cells, H 2 S increased the frequency of iberiotoxin-sensitive, Ca 2+ spark-induced transient Ca 2+ -activated K + (K Ca ) currents ∼1.83-fold, but did not alter the amplitude of these events. H 2 S did not alter the activity of single K Ca channels recorded in the absence of Ca 2+ sparks in arteriole smooth muscle cells. H 2 S increased SR Ca 2+ load ([Ca 2+ ] SR ), measured as caffeine (10 and 20 mm)-induced [Ca 2+ ] i transients, ∼1.5-fold. H 2 S hyperpolarized (by ∼18 mV) and dilated pressurized (40 mmHg) cerebral arterioles. Iberiotoxin, a K Ca channel blocker, reduced H 2 S-induced hyperpolarization by ∼51{\%}. Iberiotoxin and ryanodine, a ryanodine receptor channel inhibitor, reduced H 2 S-induced vasodilatation by ∼38 and ∼37{\%}, respectively. In summary, our data indicate that H 2 S elevates [Ca 2+ ] SR , leading to Ca 2+ spark activation in cerebral arteriole smooth muscle cells. The subsequent elevation in transient K Ca current frequency leads to membrane hyperpolarization, a reduction in global [Ca 2+ ] i and vasodilatation.",
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