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

Abstract.

The sarcoplasmic reticulum Ca²⁺-ATPase (calcium-dependent adenosine triphosphatase) transports Ca²⁺ from the myoplasm to the reticulum lumen at the expense of free energy from ATP hydrolysis. Carticaine is a local anesthetic of frequent use in dentistry which is now entering other clinical fields. We studied the action of carticaine on the sarcoplasmic reticulum (SR) skeletal muscle Ca²⁺-ATPase. SR vesicles from rabbit fast skeletal muscle were used. Carticaine inhibits the enzymatic activity. The inhibition of the enzymatic activity depends on pH, [Ca²⁺] and the presence of calcimycin. Half-maximal carticaine concentration that inhibits the ATPase activity tends to a maximal value upon increasing [Ca²⁺]. Carticaine concentrations required 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 µM [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 phosphorylation 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 permeability to Ca²⁺. Ca²⁺ efflux from preloaded vesicles is prevented by Ca²⁺ and Mg²⁺. Our results suggest that the diffusion of the local anesthetic into muscle fibers might trigger undesired effects such as sustained contraction of the masticatory muscles.