Positive inotropic effect of ryanodine on rabbit ventricular muscle: dependence on the intracellular calcium load.
Two types of electrical and mechanical responses to 1 mumol/l ryanodine, depending on the intracellular calcium load, were observed in rabbit papillary muscles. In a normal calcium solution, ryanodine induced a transient decline followed by a stable increase in the developed force (by 20 +/- 5% of the pretreatment level; n = 30) and prolonged the action potential (AP). The positive ryanodine response showed an increased time-to-peak force and was completely suppressed by 2 mumol/l nifedipine, partially blocked by 50 mumol/l tetracaine (Ca2+ release blocker), but greatly potentiated by 20 mmol/l CsCl or (-) Bay R 5414 which prolonged the AP. The prolonged time-to-peak force of the positive ryanodine response was shortened by procedures raising the content of Ca2+ in the sarcoplasmic reticulum (SR). It is suggested that the initial decline in the force amplitude results from Ca2+ leakage from the SR which is further compensated for by an elevation of both the transmembrane Ca2+ entry and intracellular Ca2+ release. In calcium overloaded myocardium, 1 mumol/l ryanodine caused irreversible contracture and dramatic AP shortening, explained by a massive Ca2+ release from the overloaded SR into the cytoplasm. It is concluded that the calcium content in the SR is the main modulator of the electrical and mechanical effects of ryanodine in ventricular myocardium.
Gainullin
R Z
RZ
Institute of Biological Physics, Academy of Sciences of the USSR, Moscow Region.
Saxon
M E
ME
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology*; D013748:Tetracaine / Q000494:pharmacology; D016276:Ventricular Function
D000470:Alkaloids; D002712:Chlorides; D013748:Tetracaine; D012433:Ryanodine; D002586:Cesium; D010042:Ouabain; C028019:cesium chloride; D009543:Nifedipine; D002118:Calcium