MgSO4 relaxes porcine airway smooth muscle by reducing Ca2+ entry

Magnesium sulfate (MgSO4) is used clinically, but its mechanism of action is unknown. To determine whether MgSO4 relaxes airway smooth muscle and to investigate the pathways involved, we compared effects of MgSO4 in porcine tracheal and bronchial muscles contracted with either carbachol or KCl and measured the effects of MgSO4 on the concentration of intracellular free calcium ([Ca2+](i)). Lungs were dissected after anesthesia and exsanguination. Tracheal strips and bronchial rings were suspended in tissue baths for measurement of isometric tension in the presence of different concentrations of MgSO4. In separate experiments, tracheal smooth muscle tension and [Ca2+](i) were measured simultaneously, using the fluorescent dye fura 2. MgSO4 (1.2, 2.2, 9.2 mM) produced a concentration-dependent rightward shift of contraction dose-response curves to KCl but not to carbachol. MgSO4 relaxed trachealis muscles precontracted with KCl or carbachol and simultaneously decreased [Ca2+](i). These findings indicate that MgSO4 directly relaxes airway smooth muscle and that the mechanism involves a decrease in [Ca2+](i). Because initiation and maintenance of contraction during KCl stimulation and maintenance of contraction during carbachol stimulation require Ca2+ entry through voltage-dependent calcium channels, MgSO4-induced relaxation may involve a decrease in Ca2+ entry via these channels.