Modulation of Ca(2+) signalling in human vascular endothelial cells by hydrogen sulfide.
Hydrogen sulfide (H(2)S) is now recognised as an important endogenous antihypertensive molecule and is synthesised in the vasculature primarily by endothelial cystathionine gamma lyase. Activity of this enzyme, and the production of other vasoactive substances by the endothelium, are subject to modulation by changes of [Ca(2+)](i). Here, we have used microfluorimetry to investigate whether H(2)S can regulate human endothelial [Ca(2+)](i). H(2)S (applied via the donor NaHS, 5-500 microM) caused concentration-dependent rises of [Ca(2+)](i) which were attributable to release from an ATP- and 4-CEP sensitive intracellular pool. Rises of [Ca(2+)](i) evoked by H(2)S were essentially abolished by prior pool depletion. In the absence of external Ca(2+), H(2)S slowed the decay phase of responses to cyclopiazonic acid, but this could not be attributed to the inhibition of Ca(2+) extrusion since the effects of H(2)S were at least additive with the Na(+)/Ca(2+) exchange inhibitors bepridil and SEA 0400 and the Ca(2+) ATPase inhibitor, carboxyeosin. In some but not all the cells, re-exposure to extracellular Ca(2+) following the addition and removal of H(2)S activated capacitative Ca(2+) entry (CCE), and H(2)S increased ATP-evoked (but not thapsigargin-evoked) CCE. Effects of H(2)S were not mediated by energy depletion or production of cyclic ADP ribose. Our data indicate that H(2)S can modulate endothelial [Ca(2+)](i) via multiple mechanisms, and such effects are likely to contribute to this gasotransmitter's beneficial actions.
Bauer
Claudia C
CC
Division of Cardiovascular and Neuronal Remodelling, Leeds Institute for Genetics Health and Therapeutics, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK.
Boyle
John P
JP
Porter
Karen E
KE
Peers
Chris
C
D000368:Aged; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged
D002120:Calcium Channel Agonists; D003542:Cystathionine gamma-Lyase; D002118:Calcium; D006862:Hydrogen Sulfide