The opposite effects of magnesium and calcium on the contraction of the guinea-pig ventricular myocardium in dependence on the sodium concentration

Abstract

1. Mg2+, in the investigated range up to 19.2 mM, produced a concentration-dependent reduction of the force of contraction (Fc) of the guinea-pig papillary muscle. Addition of 10 mM Mg2+ to a Mg2+-free bath solution diminished Fcto about 50%. 2. The duration of the action potential was slightly prolonged by 19.2 mM Mg2+ (15 ms at 90% repolarization), and the velocity of depolarization was slightly diminished (by 9%). 3. The negative inotropic effect of Mg2+ was primarily the consequence of a decrease in contraction velocity (S1), i.e., of a negative klinotropic effect. There was a 12% diminution of the time to peak force (t1) and a 13% prolongation of the relaxation time (t2) by an elevation of [Mg2+]0 up to 19.2 mM. 4. The curve representing the relation between [Ca2+]0 and contraction velocity (S1) was shifted to the right by an increase in [Mg2+]0. There was a linear dependence on Mg2+ of the calcium concentrations that were needed to sustain a definite level of S1 (equieffective [Ca2+]0). A computed regression for this dependence indicates that the negative klinotropic effect of an addition of 10 mM Mg2+ to a solution containing 2.15 mM Ca2+ and no Mg2+ will be antagonized by addition of 0.83 mM Ca2+. 5. These results are compatible with a competitive antagonism between Mg2+ and Ca2+ in regard to their binding to a hypothetical receptor. The apparent dissociation constant of the Mg2+-receptor complex would be about 25 mM in the presence of 140 mM Na+. 6. The negative klinotropic potency of Mg2+ and the positive klinotropic potency of Ca2+ were augmented to a similar degree by a reduction of [Na+]0. 7. The possibility is discussed that Na+ competes with Mg2+ and Ca2+ for a common receptor at the cellular surface. In such a case, for the condition that either 1 Mg2+, 1 Ca2+ or 2 Na+ can be bound by the receptor, the apparent dissociation constant of the Mg2+-receptor complex, as estimated by extrapolation to 0 mM Na+ would be about 6 mM.