Influence of Calcium and Magnesium Ions on the Sino-atrial Node Pacemaker Activity of the Canine Heart

Using constant pressure perfusion technique of the canine sinus node artery, effects of changing concentrations of calcium and magnesium ions were investigated on the sinoatrial (SA) pacemaker activity. An increase in calcium concentration produced a diphasic chronotropic action; positive at 5-25 mEq/liter but negative above 30 mEq/liter. The positive chronotropic action of calcium was not prevented by pretreatment with reserpine, but partially depressed by beta-adrenergic blocking agents. On the contrary, an infusion of GEDTA, more specific Ca++ chelating agent, slowed the sinus rate and further produced sinus arrhythmia at a higher infusion rate, which was restored to regular sinus rhythm by norepinephrine. Changes in magnesium concentration produced dose-dependently a negative chronotropic effect that was not modified by atropine. Positive chronotropic responses either to calcium or to isoproterenol were significantly depressed by increasing magnesium concentration. Atrial fibrillation induced by acetylcholine was facilitated by increasing calcium concentration but inhibited by administration of either magnesium or GEDTA. Antagonism between calcium and magnesium was demonstrated on the SA node pace-maker activity. It is suggested that calcium and catecholamine facilitate each other the action at the effector sites and that magnesium stabilizes the membrane of the SA node pacemaker against any stimuli of rapid firing.