Cytosolic magnesium modulates calcium channel activity in mammalian ventricular cells

Abstract

The effect of cytosolic free Mg2+ concentration on the regulation of myocardial function was studied by dialyzing isolated guinea pig ventricular myocytes with different internal Mg2+ concentrations [( Mg2+]i). We found that elevation of [Mg2+]i shortened the action potential and suppressed the Ca2+ current. Mean values recorded for action potential duration in cells dialyzed with solutions containing 0, 1.3, and 9.4 mM Mg2+ were 620 +/- 40, 400 +/- 25, and 60 +/- 10, respectively. The suppressive effect of [Mg2+]i on the action potential duration correlated significantly with the suppressive effects of [Mg2+]i on the Ca2+ current. In cells dialyzed with nominally zero Mg2+, calcium current was prominent (3.5 +/- 0.58 nA). At [Mg2+]i of 1.4 mM, calcium current was significantly smaller than in zero [Mg2+]i and was almost completely inhibited by dialysis of the cell with 9.4 mM Mg2+. The Mg2+-induced block of the Ca2+ current was due to steady-state inactivation of the high threshold calcium channel. The block was observed in the presence or absence of adenosine 3',5'-cylic monophosphate and was not reversed by elevation of external Ca2+ concentration, addition of adrenaline, or large negative potentials. These data suggest that cytosolic Mg2+ regulates Ca2+ channel activity by a novel mechanism, unrelated to its effect as a blocking particle of the open channel.

Involvement of Mg2+ in terminating Ca2+ release in cultured rat skeletal muscle

“…2E). Augmentation of Ca 2+ current in low [Mg2+]i has also been reported in cardiac muscle cells [25]. One may still argue that tail currents may contribute to terminating caffeine-induced Ca 2+ release.…”

Possible pharmacological actions of magnesium in acute myocardial infarction.

“…Inhibition of calcium channel activity by [Mg2+]i has also been reported in guinea pig ventricular myocytes, though the mechanism differs in that it is independent of ligandmediated phosphorylation (Agus et al, 1989 (Maguire, 1984;Romani & Scarpa, 1990 In summary, therefore, elevation of serum magnesium to 1.5-2.0 mm has little effect on normal cardiac electrophysiology but has been reported to reduce the frequency of clinically significant arrhythmias early after acute myocardial infarction in several controlled trials. Laboratory studies suggest that magnesium may have an anti-arrhythmic action by suppressing automaticity in partially depolarized cells and that inhibition of calcium current is likely to contribute to this effect.…”

Phosphorylation restores activity of L‐type calcium channels after rundown in inside‐out patches from rabbit cardiac cells.

“…Cukierman et al (1988) reported a 7-14 mV hyperpolarizing shift for sodium channels in response to 7-5 mm inside Ca2 . Hartzell & White reported a 10 mV hyperpolarizing shift of calcium channel activation in response to an increase from 0 3 to 3 mm inside Mg2+, although Agus et al (1989) failed to see a shift of calcium channel availability by 9-4 mm inside Mg2+. Our results support the conclusion of Hartzell & White (1989) that fixed negative charges exist on the inside of the calcium channel.…”