Different roles of ryanodine receptors and inositol (1,4,5)-trisphosphate receptors in adrenergically stimulated contractions of small arteries

The functions of ryanodine receptors (RyRs) and inositol (1,4,5)-trisphosphate receptors Ins(1,4,5)P(3)Rs] in adrenergically activated contractions of pressurized rat mesenteric small arteries were investigated. Caffeine (20 mM) but not phenylephrine (PE; 10 microM) facilitated the depletion of smooth muscle sarcoplasmic reticulum (SR) Ca(2+) stores by ryanodine (40 microM). In ryanodine-treated SR-depleted arteries, 1) Ca(2+) sparks were absent, 2) low concentrations of PE failed to elicit either vasoconstriction or normal asynchronous propagating Ca(2+) waves, and 3) high PE] induced abnormally slow oscillatory contractions (vasomotion) and synchronous Ca(2+) oscillations. In ryanodine-treated SR-depleted arteries denuded of endothelium, high PE] induced steady contraction and steady elevation of intracellular Ca(2+)]. In contrast, 2-aminoethyl diphenylborate (2-APB), a putative blocker of Ins(1,4,5)P(3)Rs, produced opposite effects to ryanodine: 1) Ca(2+) sparks were present; 2) Ca(2+) waves were absent; 3) caffeine-releasable Ca(2+) stores were intact; and 4) PE, even at high concentrations on endothelial-denuded arteries, failed to elicit contraction, asynchronous Ca(2+) waves, or synchronous Ca(2+) oscillations or maintained elevated Ca(2+)]. We conclude that 1) Ins(1,4,5)P(3)Rs are essential for adrenergically induced asynchronous Ca(2+) waves and the associated steady vasoconstriction, 2) RyRs are not appreciably opened during adrenergic activation (because PE did not facilitate the development of the effects of ryanodine), and 3) Ins(1,4,5)P(3)Rs are not essential for Ca(2+) sparks. This provides an explanation of the fact that adrenergic stimulation decreases the frequency of Ca(2+) sparks (previously reported) while simultaneously increasing the frequency of asynchronous propagating Ca(2+) waves; different SR Ca(2+)-release channels are involved.