Effects of Elevated Cytosolic Calcium on ACh-Induced Swine Tracheal Smooth Muscle Contraction

Increased intracellular calcium concentration ([Ca(2+)](i)) is required for smooth muscle contraction. In tracheal and other tonic smooth muscles, contraction and elevated [Ca(2+)](i) are maintained as long as an agonist is present. To evaluate the physiological role of steady-state increases in Ca(2+) on tension maintenance, [Ca(2+)](i) was elevated using ionomycin, a Ca(2+) ionophore or charybdotoxin, a large-conductance calcium-activated potassium channel (K(Ca)) blocker prior to or during exposure of tracheal smooth muscle strips to ACh (10(-9) to 10(-4) M). Ionomycin (5 &mgr;M) in resting muscles induced increases in [Ca(2+)](i) to 500 +/- 230 nM and small increases in force of 2.6 +/- 2.3 N/cm(2). This tension is only 10% of the maximal tension induced by ACh. Charybdotoxin had no effect on [Ca(2+)](i) or tension in resting muscle. After pretreatment of muscle with ionomycin, the concentration-response relationship for ACh-induced changes in tension shifted to the left (EC(50) = 0.07 +/- 0.05 &mgr;M ionomycin; 0.17 +/- 0.07 &mgr;M, control, p < 0.05). When applied to the muscles during steady-state responses to submaximal concentrations of ACh, both ionomycin and charybdotoxin induced further increases in tension. The same magnitude increase in tension occurs after ionomycin and charybdotoxin treatment, even though the increase in [Ca(2+)](i) induced by charybdotoxin is much smaller than that induced by ionomycin. We conclude that the resting muscle is much less sensitive to elevation of [Ca(2+)](i) when compared to muscles stimulated with ACh. Steady-state [Ca(2+)](i) limits tension development induced by submaximal concentrations of ACh. The activity of K(Ca) moderates the response of the muscle to ACh at concentrations less than 1 &mgr;M. Copyright 1996 S. Karger AG, Basel