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 [Ca^2-]_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.