Mechanism of uridine 5′‐triphosphate‐induced Ca(2+) waves in rat basilar artery

Abstract

Uridine 5′-triphosphate (UTP) is a potent vasoconstrictor and induces Ca2+ waves in cerebral arteries. We investigated the mechanism of UTP-induced Ca2+ waves in rat basilar artery using the Ca2+-sensitive dye Fluo-4 and confocal microscopy. UTP elicits cyclic increases in intracellular Ca2+ which progressively decrease in amplitude and correspond to transient force generation. Initiation of Ca2+ waves is dependent on Ca2+ release from the sarcoplasmic reticulum (SR), as blockade of the sarco(endo)plasmic reticulum Ca2+-ATPase with cyclopiazonic acid abolishes Ca2+ waves. Their initiation is not affected by inhibition of inositol 1,4,5-triphosphate receptors with 2-aminoehoxydiphenylborinate, but depletion of the ryanodine-sensitive Ca2+ stores by caffeine preincubation prior to UTP stimulation abolishes the Ca2+ waves. Finally, although blockade of L-type voltage-gated Ca2+ channels (L-VGCCs) does not affect Ca2+ waves, removal of extracellular Ca2+ significantly decreases their duration. These findings suggest that Ca2+ waves in rat basilar artery are linked to force generation and are due to repetitive cycles of Ca2+ release from the ryanodine-sensitive component of the SR, but extracellular Ca2+ influx through channels other than L-VGCCs is important for their maintenance, presumably by supplying Ca2+ for SR refilling. This work was funded by the Canadian Institutes for Health Research.