Ryanodine block of calcium oscillations in heart muscle and the sodium-tension relationship.
The control of tension is examined in cardiac Purkinje fibers. We show, in accordance with earlier results (14, 15), that tension produced by this preparation is a steep power function of intracellular sodium. With the aid of ryanodine, a pharmacological agent that blocks spontaneous and spatially asynchronous calcium release from the sarcoplasmic reticulum (SR), we investigate the influence that such calcium fluctuations have on tension. We find that even when we control for alterations of intracellular pH, the presence of such fluctuations reduces the dependence of tension on intracellular sodium. We present a simple model that can explain how the presence of oscillations of intracellular calcium leads to a reduction of the slope of the tension-calcium relationship. We show, furthermore, that when the oscillations are spatially asynchronous, this reduction of slope is even greater. The modeling takes account of the known relationships between tension and calcium and tension and sarcomere length. We conclude that the effect of ryanodine to steepen the tension-sodium relationship can be explained by ryanodine's blocking calcium release from the SR, thereby abolishing oscillations of intracellular calcium.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004553:Electric Conductivity; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D011188:Potassium / Q000502:physiology; D012433:Ryanodine / Q000494:pharmacology*; D012508:Sarcolemma / Q000502:physiology; D012756:Sheep; D012964:Sodium / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D000470:Alkaloids; D012433:Ryanodine; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D002118:Calcium