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⁺]₀ (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⁺]₀ did not decrease the slow inward current (Ic_a) and had little effect on voltage- and time-dependent outward potassium currents whether or not Ic_a was allowed to flow. 4. Zero [Mg²⁺]₀ decreased the duration, but not amplitude, of the AP. Zero [Mg²⁺]₀ had little effect on Ic_a and on outward currents except for a small increase in outward current in the region of the negative slope of the inward rectifier currentvoltage relationship. 5. In our myocytes, in contrast to [Mg²⁺]₀ high [Ca²⁺]₀ significantly increased the amplitude and decreased the duration of the AP; at the same time, high [Ca²⁺]₀ increases Ic₂. and the outward potassium current. 6. High [Mg²⁺]₀ decreased the amplitude of the oscillatory potentials (V_os) induced by various Ca₂₊-over1oading procedures (high [Ca²⁺]₀, noradrenaline, strophanthidin and barium). 7. It is concluded that the mechanisms by which high [Mg²⁺]₀ 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.