Intracellular action of magnesium in airways smooth muscle relaxation in rabbit

This study was designed to examine whether magnesium has an intracellular a ction on airways smooth muscle contraction. Tracheal muscle strips were obt ained from six male rabbits and perfused in a bathing chamber. The muscle w as incubated in Krebs solution for 15 min. Then, the bath solution was chan ged to a Ca++ free (calcium free) solution for 10 min. 10(-4) M Ach (acetyl choline) applied in the Ca++ free solution evoked a muscle contraction, at about 60% of initial contraction induced by 10 Ach in Krebs solution. Afte r control contraction, magnesium sulfate (range 10(-4) - 1 M) was applied i n Ca++ free solution. At each dose of magnesium pretreatment the response o f the muscle to 10(-4) M Ach in Ca++ free solution was measured. Magnesium caused a decrease in Ach-induced contraction in a dose-dependent manner. 10 (-1) M MgSO4 depressed to 13.28% of the contraction of Ach in Calcium free solution. The time to peak contraction and to washout, were also decreased. The concentration for 50% inhibition (IC50) of the maximal contraction was estimated to be 10(-3) M MgSO4. Re-admission of Krebs solution to muscle s trip, resulted in contraction as a consequence of massive influx of Ca++ th at occurs during the phase of Ca++ repletion. These data suggest that magne sium has an intracellular action and inhibits smooth muscle contraction in a Ca++ free solution probably by inhibiting Ca++ release from the sarcoplas mic reticulum.