THE EFFECTS OF VARIOUS DRUGS ON CALCIUM EXCHANGE IN THE ISOLATED GUINEA-PIG LEFT AURICLE

A study was made of the effects of acetylcholine, adenosine, ryanodine, norepinephrine and strophanthin-K on total calcium content and calcium exchange (during 5-minute exposures to Ca 45 ) in isolated guinea-pig left auricles. No significant change in total calcium content was associated with the change in contractile strength produced by any of these drugs, with the exception of a small decrease in the case of adenosine, which was probably fortuitous. Both acetylcholine and adenosine, at concentation which depressed contraction strength about 80%, significantly reduced the exchange of calcium associated with contraction. Atropine blocked the effects of acetylcholine on both contractility and exchange. Ryanodine, a cardiac depressant with a slower onset of action than acetylcholine and adenosine, caused no detectable change in calcium exchange even though a sufficient concentration was used to cause a depression of contractility almost as great as that produced by the other two drugs. Norepinephrine and strophanthin-K were both shown to cause significant increases in the exchange of calcium associated with contraction during the course of their positive inotropic effects. Modifications of the usual experimental procedure were employed to demonstrate these increases. During the terminal toxic action of strophanthin-K both contractility and exchange of calcium were markedly decreased. Neither norepinephrine nor strophanthin-K altered calcium exchange in quiescent auricles. The results have been discussed from the standpoint of a contraction-dependent exchange of extracellular calcium with a limited fraction of the cellular calcium, termed the "contraction pool." The results in general are in agreement with the concept that calcium is intimately associated with contraction. However, the causal relationship between drug action and calcium exchange remains obscure.