Effects of lidocaine on intracellular Ca2+ and tension in airway smooth muscle

Abstract

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 μM acetylcholine (ACh)-induced contraction, the cumulative application of lidocaine (10-6 ~ 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 μM ACh, the [Ca2+](i)-tension relationship shifted markedly to the left, thereby indicating an increase in Ca2+ sensitivity of the contractile 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 μM 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+.