Halothane counteracts acetylcholine-induced increase in Ca2+ sensitivity of the contractile apparatus in airway smooth muscle.

The direct relaxing effect of halothane on airway smooth muscle has been reported to involve the reduction of the cytosolic Ca2+ concentration ([Ca2+]i) and the [Ca2+]i-independent inhibitory mechanism. To clarify the extent of the contribution of these mechanisms, the effect of halothane on the [Ca2+]i-tension relationship in porcine tracheal smooth muscle strips was evaluated, using fura-2 fluorometry. The control [Ca2+]i-tension relationship was constructed from data of [Ca2+]i and tension during the contractions induced by the stepwise increment of extracellular Ca2+ concentrations under high K+ depolarization. In the presence of acetylcholine (1 microM), the [Ca2+]i-tension relationship shifted upward, which indicated the acetylcholine-induced increase in the Ca2+ sensitivity of the contractile apparatus. Halothane (0.034 mM), in the absence of acetylcholine, did not alter the increases in either [Ca2+]i or tension, hence no change in the [Ca2+]i-tension relationship. However, in the presence of acetylcholine, halothane did attenuate the acetylcholine-induced upward shift of the [Ca2+]i-tension relationship. Halothane proved to have a potent attenuating effect on the acetylcholine-induced increase in Ca2+ sensitivity of the contractile apparatus with little influence on [Ca2+]i. This desensitization of the contractile apparatus to [Ca2+]i may play a major role in the direct airway relaxing effect of halothane.