Smooth muscle contraction and local anesthetics: calmodulin-dependent myosin light-chain kinase

Myocardial depressant action of local anesthetics at toxic concentrations is well documented. Their effect on vascular smooth muscle, however, remains controversial. This study analyzed local anesthetic action on the subcellular smooth-muscle contractile system. Highly purified smooth-muscle myosin and myosin light-chain kinase (MLCK) were prepared from fresh turkey gizzards, and the phosphorylation of the myosin light-chain in the presence of Ca++ and calmodulin was evaluated by the urea gel-electrophoresis. Tetracaine 1.3.10(-3) M and bupivacaine 7.5.10(-3) M inhibited the MLCK 50%, whereas lidocaine 2.5.10(-2) M inhibited the MLCK 40%. The inhibitory action was partially reversed by increasing the calcium ion concentration from 1.10(-5) to 2.10(-4) M. On the other hand, raising the calmodulin concentration from 1.10(-7) M to 6.10(-7) M completely reversed the inhibition. A possible cause of the discrepancy in the anesthetic concentrations between subcellular and in vivo studies is discussed.