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The neutral alkaloid, ryanodine, has several actions on cardiac muscle. To delineate better its mode of action, we studied ryanodine's effect upon contracting cat papillary muscles under changing loading conditions and stimulation frequencies. We also studied ryanodine's physiologic and metabolic effects upon isolated rat hearts. The results of our study suggest the following: (1) ryanodine causes both decreased release and decreased uptake of calcium by the sarcoplasmic reticulum; (2) elevation of high-energy phosphates secondary to decreased energy requirements is due to decreased calcium availability to the myofilaments during systole; (3) the slowed or incomplete relaxation caused by ryanodine may be a stimulus for myosin phosphorylation; (4) ryanodine probably decreases calcium movement through the sarcolemma and so increases adenosine and inorganic phosphate and decreased cyclic adenosine monophosphate (AMP) concentration in the myocardium; and (5) the effect of ryanodine on altered loading conditions and contraction velocities can be understood in terms of decreased calcium availability to the myofilaments.
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