Different roles of ryanodine receptors and inositol (1,4,5)-trisphosphate receptors in adrenergically stimulated contractions of small arteries
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2004
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Abstract
The functions of ryanodine receptors (RyRs) and inositol (1,4,5)-trisphosphate receptors [Ins(1,4,5)P3Rs] in adrenergically activated contractions of pressurized rat mesenteric small arteries were investigated. Caffeine (20 mM) but not phenylephrine (PE; 10 μM) facilitated the depletion of smooth muscle sarcoplasmic reticulum (SR) Ca2+ stores by ryanodine (40 μM). In ryanodine-treated SR-depleted arteries, 1) Ca2+ sparks were absent, 2) low concentrations of PE failed to elicit either vasoconstriction or normal asynchronous propagating Ca2+ waves, and 3) high [PE] induced abnormally slow oscillatory contractions (vasomotion) and synchronous Ca2+ oscillations. In ryanodine-treated SR-depleted arteries denuded of endothelium, high [PE] induced steady contraction and steady elevation of intracellular [Ca2+]. In contrast, 2-aminoethyl diphenylborate (2-APB), a putative blocker of Ins(1,4,5)P3Rs, produced opposite effects to ryanodine: 1) Ca2+ sparks were present; 2) Ca2+ waves were absent; 3) caffeine-releasable Ca2+ stores were intact; and 4) PE, even at high concentrations on endothelial-denuded arteries, failed to elicit contraction, asynchronous Ca2+ waves, or synchronous Ca2+ oscillations or maintained elevated [Ca2+]. We conclude that 1) Ins(1,4,5)P3Rs are essential for adrenergically induced asynchronous Ca2+ 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)P3Rs are not essential for Ca2+ sparks. This provides an explanation of the fact that adrenergic stimulation decreases the frequency of Ca2+ sparks (previously reported) while simultaneously increasing the frequency of asynchronous propagating Ca2+ waves; different SR Ca2+-release channels are involved.
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wier2004americandifferent
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| Authors | Christine Lamont,W. Gil Wier;Christine Lamont;W. Gil Wier; |
| Journal | american journal of physiology-heart and circulatory physiology |
| Year | 2004 |
| DOI |
10.1152/ajpheart.00708.2003
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