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Inhibition by magnesium of calcium inward current in heart ventricular muscle
1Institut für Pharmakologie und Toxikologie, Technischen Universität München, F.R.G.
Abstract:
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 depolarization 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.
Insights
Magnesium reduces heart muscle contraction by inhibiting calcium currents. This effect depends on voltage, with magnesium increasing inward currents at negative potentials.
Area of Science:
- Cardiology
- Electrophysiology
- Pharmacology
Background:
- Magnesium plays a crucial role in cardiac function.
- The negative inotropic effect of magnesium suggests an impact on ion currents in heart muscle cells.
Purpose of the Study:
- To investigate if magnesium's negative inotropic effect in mammalian ventricular muscle is caused by inhibition of the calcium inward current.
- To elucidate the voltage-dependence of magnesium's effect on ion currents.
Main Methods:
- Whole-cell voltage-clamp experiments were performed on isolated guinea-pig heart cells.
- Sodium inward current was inactivated using a conditioning pre-pulse or tetrodotoxin.
- Magnesium concentration-dependent effects on calcium and sodium currents were analyzed.
Main Results:
- Magnesium diminished the calcium inward current in a concentration-dependent and reversible manner (approx. 45% reduction with increased magnesium).
- Inhibition was primarily due to reduced maximal calcium current and a shift in the current-voltage relationship.
- Magnesium increased inward currents at negative potentials (<-40 mV), likely due to incomplete sodium current inactivation.
Conclusions:
- Magnesium's negative inotropic effect is significantly mediated by the inhibition of the calcium inward current.
- The interaction of magnesium with ion channels is voltage-dependent, influencing both calcium and sodium currents.