Ryanodine alteration of the contractile state of rat ventricular myocardium. Comparison with dog, cat, and rabbit ventricular tissues.

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Abstract
To test the hypothesis that ryanodine inhibits the release of contractile Ca2+ from intracellular stores, the contractile responses by rabbit, cat, dog and rat papillary muscles to ryanodine were compared. Results of cumulative ryanodine concentration (10-9-10-4 M) response studies indicate the following order of sensitivity of ryanodine: rat > dog = cat > rabbit which mimics the relative dependence of these species on intracellular Ca2+ for force development. In the presence of 2.5 mM [Ca2+]o [extracellular Ca2+ concentration], cumulative additions of ryanodine or a single exposure to 10-4 M concentration produced biphasic contractile responses in rabbit, cat and dog, but not rat ventricular muscle. The elevation of [Ca2+]o to 5 mM antagonized the expression of ryanodine''s negative inotropic effect or promoted the positive effect of this agent in all species tested. Ryanodine did produce a biphasic change in contractility in the presence of 2.5 mM [Ca2+]o in K+-depolarized, isoproterenol-restored rat papillary muscles. Prior exposure of rat myocardium to ryanodine (2.5 mM [Ca2+]o) was similar to a decreased [Ca2+]o in that it permitted inotropic agents, e.g., increased stimulation rates, hyperosmolality and ouabain to produce positive contractile responses from this tissue. The positive response by rat cardiac muscle to paired electrical stimulation is prevented by ryanodine. Ryanodine accelerated the rest-decay of force development in rat myocardium, suggesting that it increased the rate of loss of Ca from contractile-dependent Ca2+ stores. Apparently ryanodine effects a decreased availability of intracellular contractile Ca2+, perhaps through a diminishment of its release.