On the antiarrhythmic actions of magnesium in single guinea-pig ventricular myocytes

1. The hypotheses that magnesium quickly abolishes arrhythmias by acting as a calcium antagonist or by increasing outward potassium currents were tested in guinea-pig isolated ventricular myocytes by recording membrane potentials and currents by means of a single microelectrode discontinuous voltage clamp method. 2. High [Mg2+](o) (4-16 mmol/L) slightly increased the amplitude and duration of the action potential (AP) in some myocytes, but overall the changes were not significant, 3. High [Mg2+](o) did not decrease the slow inward current (I-Ca) and had little effect on voltage- and time-dependent outward potassium currents whether or not I-Ca was allowed to flow. 4. Zero [Mg2+](o) decreased the duration, but not amplitude, of the AP. Zero [Mg2+](o) had little effect on I-Ca and on outward currents except for a small increase in outward current in the region of the negative slope of the inward rectifier current-voltage relationship. 5. In our myocytes, in contrast to [Mg2+](o), high [Ca2+](o) significantly increased the amplitude and decreased the duration of the AP; at the same time, high [Ca2+](o) increases I-Ca and the outward potassium current. 6. High [Mg2+](o) decreased the amplitude of the oscillatory potentials (V-os) induced by various Ca2+-overloading procedures (high [Ca2+](o), noradrenaline, strophanthidin and barium). 7. It is concluded that the mechanisms by which high [Mg2+](o) quickly suppresses cardiac arrhythmias are related to an extracellular action of Mg2+ and do not include a block of I-Ca or an increase in outward current. Mg2+ can be antiarrhythmic by decreasing V-os amplitude and possibly by screening the fixed negative charges at the external surface of the sarcolemma.