Role of calcium channel blockade in relaxation of tracheal smooth muscle by extracellular Mg2+.

Abstract

Magnesium ion (Mg2+) is a bronchodilator, but little is known about its mechanism of action on airways. We hypothesized that Mg2+ inhibits voltage-dependent Ca2+ channels of airway smooth muscle. Smooth muscle cells were freshly dispersed from pig trachea with collagenase. Depolarization-induced inward Ca2+ currents, measured in whole cell patch-clamp experiments, were inhibited by nifedipine and stimulated by BAY K 8644. Increasing bath Mg2+ from 1 to 21 mM caused a reversible approximately 30% inhibition of current and a positive shift of the peak current-voltage relationship. Voltage-dependent steady-state inactivation had a half-maximal potential (Vh) of -12 mV and a Boltzmann slope factor (k) of 6.0 mV. High Mg2+ caused a positive shift in Vh without affecting k, whereas nifedipine caused a negative shift in Vh and increased k. The inhibition of voltage-dependent Ca2+ channel currents by Mg2+ was quantitatively similar to Mg(2+)-induced relaxation of KCl-contracted tracheal smooth muscle strips. We conclude that inhibition of Ca2+ influx through dihydropyridine-sensitive, voltage-dependent channels by Mg2+ accounts for much of its relaxant action on airway smooth muscle.