title: Hydrogen sulfide activates Ca²⁺ sparks to induce cerebral arteriole dilatation.
abstract: 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.
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Guo Hua
authors.initials: GH
authors.lastname: Liang
authors.forename: Qi
authors.initials: Q
authors.lastname: Xi
authors.forename: Charles W
authors.initials: CW
authors.lastname: Leffler
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Jaggar
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D024681:Potassium Channels, Calcium-Activated; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium; D006862:Hydrogen Sulfide