Handling of Cytoplasmic Ca2+ by the Sarcoplasmic Reticulum during α1-Adrenoceptor-Mediated Contraction of Rat Mesenteric Resistance Arteries

Abstract

We investigated the role of the sarcoplasmic reticulum (SR) in the regulation of cytoplasmic Ca2+ ([Ca2+]i) during alpha 1-adrenoceptor-mediated contraction in rat mesenteric resistance arteries. Phenylephrine (PE) at 1 microM elevated the tension and [Ca2+]i measured with fura-2 in Ca(2+)-containing PSS, but did not do so in Ca(2+)-free PSS, suggesting that the contraction elicited by this concentration depends on the Ca2+ influx. Caffeine (100 mM) was shown to discharge Ca2+ in the SR, and cyclopiazonic acid (CPA, 10 microM) was shown to inhibit the Ca2+ uptake into the SR in these arteries. In resting arteries, both CPA and ryanodine (10 microM) sustainedly elevated [Ca2+]i without affecting the tension. In PE-stimulated arteries, both agents caused transient increase in [Ca2+]i, which was larger than that in resting arteries, and augmented the contraction. In the presence of PE, the caffeine-evoked [Ca2+]i transient was more greatly decreased after the application of ryanodine than after CPA. The CPA-induced rise in [Ca2+]i could be ascribed to inhibition of Ca2+ buffering by the SR, and the ryanodine-induced one can be attributed to the acceleration of Ca2+ release. It is suggested that both Ca2+ release from and Ca2+ uptake into the SR are enhanced during PE-induced contraction, which depends on the transmembrane Ca2+ influx.