EFFECTS OF LIDOCAINE ON INTRACELLULAR CA-2-MUSCLE( AND TENSION IN AIRWAY SMOOTH)

Background: Many studies have demonstrated that lidocaine directly rel axes airway smooth muscle. The underlying mechanisms, especially in re lation to Ca2+ mobilization, remain to be elucidated. Methods: Using f ront-surface fluorometry and fura-2-loaded porcine tracheal smooth mus cle strips, intracellular Ca2+ concentration ([Ca2+]i) and isometric t ension were simultaneously measured. Results. In cases of 40 mm K+-ind uced contraction and 1 mum acetylcholine (ACh)-induced contraction, th e cumulative application of lidocaine (10(-6) approximately 3 X 10(-3) m) caused a concentration-dependent decrease in [Ca2+]i and tension, and almost complete relaxation. To examine the effect of lidocaine on Ca2+ sensitivity of the contractile apparatus, the [Ca2+]i-tension rel ationship was determined by changing the extracellular Ca2+ concentrat ion during 40 mm K+ induced depolarization, with and without treatment with lidocaine. Although treatment with 1 mm lidocaine inhibited incr eases in both [Ca2+]i and tension induced by extracellular Ca2+, it ha d little effect on the [Ca2+]i-tension relationship. In the presence o f 1 mum ACh, the [Ca2+]i-tension relationship shifted markedly to the left, thereby indicating an increase in Ca2+ sensitivity of the contra ctive apparatus; this shift was inhibited by 1 mm lidocaine. In the ab sence of extracellular Ca2+, 1 mm lidocaine inhibited the release of s tored Ca2+ induced by 1 mum ACh, but not that by 20 mm caffeine. Concl usions. Lidocaine directly relaxes airway smooth muscle by decreasing [Ca2+]i. In addition, lidocaine inhibits the ACh-induced increase of C a2+ sensitivity of the contractile apparatus, although it has little e ffect on Ca2+ sensitivity during high K+ depolarization. The decrease in [Ca2+]i is attributed to inhibition of the influx of extracellular Ca2+, as induced by high K+ depolarization and by ACh, and to the inhi bition of the ACh-induced release of stored Ca2+.