1. Despite widespread use of magnesium ion (Mg2+) for antiarrhythmic purposes, little direct information is available regarding its antiarrhythmic mechanisms. To elucidate the possible cellular mechanism, the effects of Mg2+ on early afterdepolarization (EAD), delayed afterdepolarization (DAD), triggered activity (TA), transient inward current (TI) and aftercontraction (AC) were examined in various cardiac preparations. The effects of Mg2+ on myoplasmic Ca2+ concentration were also studied.
2. The effects of Mg2+ on AC, induced by overdrive stimulation, were studied in isolated rat ventricular papillary muscle superfused with low K+ solution. In enzymatically isolated guinea pig myocytes, EAD, DAD and/or TA were induced after overdrive stimulation under conditions of superfusion with low K+ solution, using the whole-cell current-clamp method, and TI was also induced by the whole cell voltage clamp method.
3. Immediately after changing the solutions, containing varying concentrations of Mg2+, the effects of Mg2+ were examined. In addition, effects of Mg2+ on Ca transient were studied, using fura-2.
4. We found that: (1) in the rat papillary muscle, 10 mM Mg2+ effectively inhibited AC, which was produced after stimulation at both 3.3 Hz and 5 Hz, although 5 mM Mg2+ was without effect in the case of AC induced after 5-Hz stimulation; (2) in the myocytes, 5 mM Mg2+ did not inhibit DADs, EADs and TA, but 10 mM Mg-2 divided by inhibited them completely; (3) the amplitude and frequency of TI decreased significantly in the presence of 10 mM Mg2+; and finally (4) 10 mM Mg2+ inhibited the Ca transient underlying DAD and/or TA.
5. The findings suggest, but do not prove unequivocally, that Mg's actions are probably due to a combination of a shift of the threshold of various ion channels to less negative potentials, a decrease in Ca2+ influx via Ca channels, a block of several K channels, and/or a block of Na-Ca exchanger. In conclusion, the present study indicates that extracellular Mg2+, via whatever mechanism, exerts antiarrhythmic activities. (C) 1998 Elsevier Science Inc.
