Effect of ryanodine in dog mesenteric artery: Interference with potassium and adrenergic stimulation

Abstract

Ryanodine, a selective pharmacological tool affecting sarcoplasmic reticulum Ca2+-release channels in skeletal and cardiac muscles, was tested on contractions induced in the dog mesenteric artery by high-KCl depolarization and α-adrenergic stimulation. Ryanodine significantly potentiated tonic contractions induced by low-KCl (25-45 mM) and norepinephrine (30 nM-3 μM) stimulations. KCl potentiation was only partly sensitive to nifedipine and norepinephrine potentiation to prazosin. Tonic contractions produced by stimulation with higher KCl and norepinephrine concentrations were not potentiated, but rather attenuated, by ryanodine. In Ca2+-free medium containing 100 μM EGTA, norepinephrine induced a dose-dependent transient contraction, which was decreased or abolished by ryanodine. When repeated in Ca2+-free solutions, norepinephrine-induced transient contractions rapidly decreased in amplitude and disappeared within four consecutive stimulations. Ryanodine accelerated the rate of decay of these serial norepinephrine stimulations. These results are consistent with the interpretation that ryanodine impairs the buffering capacity of internal Ca2+ sinks, probably by making the sarcoplasmic reticulum permeable to Ca2+.