Ryanodine reveals multiple contractile and relaxant mechanisms in vascular smooth muscle: simultaneous measurements of mechanical activity and of cytoplasmic free Ca2+ level with fura‐2

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Abstract
1 The effects of ryanodine on changes in cytoplasmic Ca2+ level ([Ca2+]i) and muscle tension induced by maximum concentrations of phenylephrine (Phe; 1μm), prostaglandin F2α (PGF2α, 10 μm), caffeine (Caf, 30 mm) and isoprenaline (Iso, 1 μm) were examined in rat aortic strips using fura-2. 2 In normal media, Phe and PGF2α produced a phasic contraction, followed by a tonic one. Caf elicited only a transient contraction. When the preparation was treated with 10 μm ryanodine, an increase in [Ca2+]i was induced accompanied by a nicardipine (1 μm)-resistant contraction which was [Ca2+]o-dependent. 3 In Ca2+-free solution, the three stimulants elicited transient increases in [Ca2+]i. Transient contractions to Phe and Caf were accompanied by changes in [Ca2+]i. The transient increase in [Ca2+]i induced by PGF2α was not accompanied by a corresponding contraction. 4 Sustained contractions were induced by Phe and PGF2α in the absence of external Ca2+, while the increase in [Ca2+]i was reduced. A larger maximum contraction was induced by PGF2α than by Phe. 5 Ryanodine abolished both the Caf- and Phe-induced [Ca2+]i transient increases and the corresponding contractions, but had no substantial effect on the PGF2α-induced [Ca2+]i transient increase. Ryanodine had no influence on the sustained contractions induced by Phe and PGF2α. 6 Iso relaxed both sustained contractions almost completely, without any detectable change in [Ca2+]i. Treatment of the preparation with ryanodine had no effect on the concentration-response curves for Iso in relaxing the 0.1 μm Phe- or 40 mm K+-induced precontraction. 7 It is suggested that Phe and Caf mobilize Ca2+ from a ryanodine-sensitive Ca2+ store and that PGF2α releases Ca2+ from a ryanodine-insensitive Ca2+ store. The former contributes to the transient contraction through a Ca2+-dependent process, while the latter seems not to be directly associated with the contraction. The sustained contraction under Ca2+-free conditions might involve a Ca2+-independent process or a change in the sensitivity of the contractile filaments to Ca2+. 8 In addition to lowering cytoplasmic Ca2+ concentration, it is suggested that Iso counteracts the apparently Ca2+-independent process. The ryanodine-sensitive Ca2+ store plays no substantial role in active relaxation by Iso, although it does play a major role in the maintenance of cytoplasmic Ca2+ in a quiescent muscle.

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