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

Background: Many studies have demonstrated that lidocaine directly relaxes airway smooth muscle. The underlying mechanisms, especially in relation to Ca2+ mobilization, remain to be elucidated. Methods: Using front-surface fluorometry and fura-2-loaded porcine tracheal smooth muscle strips, intracellular Ca2+ concentration ([Ca2+]i) and isometric tension were simultaneously measured. Results. In cases of 40 mm K+-induced contraction and 1 mum acetylcholine (ACh)-induced contraction, the 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 relationship was determined by changing the extracellular Ca2+ concentration during 40 mm K+ induced depolarization, with and without treatment with lidocaine. Although treatment with 1 mm lidocaine inhibited increases in both [Ca2+]i and tension induced by extracellular Ca2+, it had little effect on the [Ca2+]i-tension relationship. In the presence of 1 mum ACh, the [Ca2+]i-tension relationship shifted markedly to the left, thereby indicating an increase in Ca2+ sensitivity of the contractive apparatus; this shift was inhibited by 1 mm lidocaine. In the absence of extracellular Ca2+, 1 mm lidocaine inhibited the release of stored Ca2+ induced by 1 mum ACh, but not that by 20 mm caffeine. Conclusions. Lidocaine directly relaxes airway smooth muscle by decreasing [Ca2+]i. In addition, lidocaine inhibits the ACh-induced increase of Ca2+ sensitivity of the contractile apparatus, although it has little effect 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 inhibition of the ACh-induced release of stored Ca2+.