Effect of carticaine on the sarcoplasmic reticulum Ca2+-dependent adenosine triphosphatase

The sarcoplasmic reticulum CA(2+)-ATPASE (calcium-dependent adenosine triph osphatase) transports CA(2+) from the myoplasm to the reticulum lumen at th e expense of free energy from ATP hydrolysis. Carticaine is a local anesthe tic of frequent use in dentistry which is now entering other clinical field s. We studied the action of carticaine on the sarcoplasmic reticulum (SR) s keletal muscle CA(2+)-ATPase. SR vesicles from rabbit fast skeletal muscle were used. Carticaine inhibits he enzymatic activity. The inhibition of the enzymatic activity depends on pH, [Ca2+] and the presence of calcimycin. H alf-maximal carticaine concentration that inhibits the ATPase activity tend s to a maximal value upon increasing [Ca2+]. Carticaine concentrations requ ired to inhibit the enzymatic activity at myoplasmic calcium concentration are lower than usual clinical doses: K-i=6.0+/-1.4 mM carticaine (n=5) for 0.1 muM [Ca2+]. ATP-dependent calcium uptake is also inhibited by the local anesthetic:K-i=30.5+/-3.4 mM (n=4). Besides, carticaine inhibits the phosp horylation of the enzyme by inorganic phosphate (Pi): K-i=20.0+/-3.4 (n=5) - 33.2+/-4.6 (n=4) mM, for [Pi] 1-4 mM. Carticaine increases the membrane p ermeability to Ca2+. Ca2+ efflux from preloaded vesicles is prevented by Ca 2+ and Mg2+. Our results suggest that the diffusion of the local anesthetic into muscle fibers might trigger undesired effects such as sustained contr action of the masticatory muscles.