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 (ICa) and had little effect on voltage- and time-dependent outward potassium currents whether or not ICa was allowed to flow. 4. Zero [Mg2+]o decreased the duration, but not amplitude, of the AP. Zero [Mg2+]o had little effect on ICa 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 ICa and the outward potassium current. 6. High [Mg2+]o decreased the amplitude of the oscillatory potentials (Vos)induced by various Ca(2+)-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 ICa or an increase in outward current. Mg2+ can be antiarrhythmic by decreasing Vos amplitude and possibly by screening the fixed negative charges at the external surface of the sarcolemma.