Inhibition by magnesium of calcium inward current in heart ventricular muscle

It was investigated whether the negative inotropic effect of magnesium in mammalian heart ventricular muscle is due to inhibition of the calcium inward current. Whole-cell voltage-clamp experiments were carried out with isolated guinea-pig heart cells. The sodium inward current was inactivated by a conditioning pre-pulse or by addition of tetrodotoxin. Magnesium concentration dependently and reversibly diminished the calcium inward current (by about 45% after an increase in magnesium concentration, from 1.2 to 9.6 mM). The decrease was mainly due to diminution of the maximally available calcium inward current but was additionally due to a shift of the current-voltage relationship to more positive potentials. The crucial dependence of the inhibition of the inward current on the pre-pulse potential was demonstrated. Conditioning dennlarization to potentials more negative than -40 mV led to an increase of an inward current by magnesium. This was probably the consequence of incomplete inactivation of the sodium current and the shift of its current-voltage relationship by the divalent cation.