Role of intracellular Ca(2+) release in histamine-induced depolarization in rabbit middle cerebral artery

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.