The Effect of Magnesium on Halothane-Induced Intracellular Calcium Concentration Changes in Cardiomyocytes

Background: Halothane, a potent inhalational anesthetic, is known to cause arrhythmia, probably due to Ryanodine Receptor (RyR) activation, triggering Ca2+ release from sarcoplasmic reticulum (SR) to the cytosol. Mg2+ hypothetically prevents Ca2+ release by inhibiting RyR and increasing Ca2+ reuptake to SR. Methods: An in vitro experiment was done on cultured cell of rat cardiomyocytes. Cells were divided into six groups. Five groups were exposed to 2 mM halothane (1-3 MAC) for 5 minutes and one was not. Of the 5 halothane-exposed groups, group 1 received no additional treatment and was observed at minute-0, 5, 10, 15 and 20 after discontinuation. Group 2 and 3 received 11 mM and 22 mM MgSO4 after halothane exposure, respectively. Group 4 and 5 received corresponding MgSO4 treatment before exposure. Cytosolic Ca2+ change was observed by a confocal microscope and emission was measured by pixel analysis. Results: Halothane increased cytosolic Ca2+ concentration in rat cardiomyocytes, in which was not substantially altered by MgSO4 given before or after the exposure. Higher dose of Mg2+ resulted in decreasing Ca2+ concentration. 22 mM MgSO4 decreased cytosolic Ca2+ concentration to the same extent as halothane discontinuation for 10 minutes. Fifteen minutes halothane discontinuation significantly decreased cytosolic Ca2+ concentration and 20 minutes discontinuation returned the Ca2+ concentration to the basal level. Conclusion: Halothane increases cytosolic Ca2+ concentration in rat cardiac myocytes. Neither pre-nor post-halothane exposure administration of MgSO4 substantially alters this phenomenon. Discontinuation of halothane for 15 minutes significantly reduces cytosolic Ca2+ concentration.