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 α₁-adrenoceptor-mediated contraction in rat mesenteric resistance arteries. Phenylephrine (PE) at 1 μM elevated the tension and [Ca²⁺]_i measured with fura-2 in Ca²⁺-containing PSS, but did not do so in Ca²⁺-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 μM) was shown to inhibit the Ca²⁺ uptake into the SR in these arteries. In resting arteries, both CPA and ryanodine (10 μM) 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.