title: Role of intracellular Ca(2+) release in histamine-induced depolarization in rabbit middle cerebral artery.
abstract: The role of Ca(2+) mobilization from intracellular stores and Ca(2+)-activated Cl(-) channels in caffeine- and histamine-induced depolarization and contraction of the rabbit middle cerebral artery has been studied by recording membrane potential and isometric force. Caffeine induced a transient contraction and a transient followed by sustained depolarization. The transient depolarization was abolished by ryanodine, DIDS, and niflumic acid, suggesting involvement of Ca(2+)-activated Cl(-) channels. Histamine-evoked transient contraction in Ca(2+)-free solution was abolished by ryanodine or by caffeine-induced depletion of Ca(2+) stores. Ryanodine slowed the development of depolarization induced by histamine in Ca(2+)-containing solution but did not affect its magnitude. In arteries treated with 1 mM Co(2+), histamine elicited a transient depolarization and contraction, which was abolished by ryanodine. DIDS and niflumic acid reduced histamine-evoked depolarization and contraction. Histamine caused a sustained depolarization and contraction in low-Cl(-) solution. These results suggest that Ca(2+) mobilization from ryanodine-sensitive stores is involved in histamine-induced initial, but not sustained, depolarization and contraction. Ca(2+)-activated Cl(-) channels contribute mainly to histamine-induced initial depolarization and less importantly to sustained depolarization, which is most likely dependent on activation of nonselective cation channels.
authors.affiliation: Department of Pharmacology, College of Medicine, The University of Vermont, Burlington 05405, USA. gokina@salus.med.uvm.edu
authors.forename: N I
authors.initials: NI
authors.lastname: Gokina
authors.forename: J A
authors.initials: JA
authors.lastname: Bevan
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D002712:Chlorides / Q000494:pharmacology; D004594:Electrophysiology; D006632:Histamine / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D009544:Niflumic Acid / Q000494:pharmacology; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D014662:Vasoconstrictor Agents; D012433:Ryanodine; D002110:Caffeine; D009544:Niflumic Acid; D006632:Histamine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium