title: Effects of Mg2+ on Ca2+ waves and Ca2+ transients of rat ventricular myocytes.
abstract: It has been shown that the occurrence of the transient inward current, which is responsible for triggered activity, was often associated with propagating regions of increased intracellular Ca2+ concentration ([Ca2+]i), i.e., the "Ca2+ wave." To investigate the mechanism of antiarrhythmic action of Mg2+, we have studied effects of high concentrations of Mg2+ on Ca2+ waves in isolated rat ventricular myocytes. [Ca2+]i was estimated using the Ca(2+)-indicating probe indo 1. Ca2+ waves in myocytes, stimulated at 0.2 Hz, were induced by perfusion of isoproterenol (10(-7) M). High Mg2+ concentration suppressed Ca2+ waves in a concentration-dependent manner (36% at 4 mM, 70% at 8 mM, and 82% at 12 mM). The Ca2+ channel blocker verapamil also suppressed Ca2+ waves in a similar way. In contrast with marked depression of Ca2+ transients by verapamil, Ca2+ transients were not affected by high Mg2+ concentration (8 mM). High Mg2+ concentration also reduced frequencies of Ca2+ waves in the absence of electrical stimulation, whereas verapamil failed to reduce frequencies of Ca2+ waves. Reduction in frequency of Ca2+ waves by high Mg2+ concentration was associated with slowing of propagation velocity of Ca2+ waves. To examine whether suppressive effects of high Mg2+ concentration on Ca2+ waves were related to an increase in intracellular Mg2+ concentration ([Mg2+]i), the effect of high-Mg2+ solution on [Mg2+]i was examined in myocytes loaded with mag-fura 2. An increase in extracellular Mg2+ concentration from 1 to 12 mM increased [Mg2+]i from 1.06 +/- 0.16 to 1.87 +/- 0.22 mM (P < 0.01) in 30 min. To examine the effect of high Mg2+ concentration on amount of releasable Ca2+ in the sarcoplasmic reticulum, the effect of high Mg2+ concentration on the Ca2+ transient induced by a rapid application of caffeine was examined. High-Mg2+ solution increased the peak of the caffeine-induced Ca2+ transient. These results suggest that the inhibitory effect of Mg2+ on Ca2+ waves was not due to inhibition of the sarcolemmal Ca2+ channel but could be due to a decreased propensity for the sarcoplasmic reticulum to divest itself of excess Ca2+.
authors.affiliation: Third Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Terada
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.forename: N
authors.initials: N
authors.lastname: Noda
authors.forename: H
authors.initials: H
authors.lastname: Satoh
authors.forename: H
authors.initials: H
authors.lastname: Katoh
authors.forename: N
authors.initials: N
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D006352:Heart Ventricles / Q000378:metabolism*; D007211:Indoles; D017136:Ion Transport / Q000187:drug effects; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D005456:Fluorescent Dyes; D007211:Indoles; D010726:Phosphodiesterase Inhibitors; D002110:Caffeine; D014700:Verapamil; D008274:Magnesium; C048960:indo-1; D002118:Calcium