Dantrolene Effect on Lidocaine-Inhibited SERCA2a From Medial Pterygoid Muscle.

Objectives: To test the effect of the calcium release blocker dantrolene on lidocaine-inhibited SERCA2a (Sarco-endoplasmic reticulum Ca-ATPase) from medial pterygoid muscle.
Methods: Pilot analytical experimental in vitro study. Rabbit (n=6) SERCA2a was isolated from medial pterygoid muscle by ultracentrifugation and chromatography (HPLC). SERCA2a activity was assayed (n=5) at variable lidocaine (0-90 mM), dantrolene (0-200 mM) and determined in media (pH7.2, 37^oC) with 3 mM ATP and MgCl₂, 100 mM KCl, 0.1 mM Ca-EGTA, 10 mM calcimycin and SERCA2a sealed vesicles (pre-equilibrated with 1 mM Ca), using a colorimetric method. Mean and SD of lidocaine IC50 and dantrolene EC50 were obtained. Student's t test was used to assess differences in SERCA2a activity (p < 0.05).
Results: Lidocaine IC50 was 20 ± 1.3 mM and Dantrolene EC50 was 112 ± 8.4 mM for each of the drugs separately. At the lidocaine IC50, SERCA2a activity was 125 ± 10 mmol Pi.mg^-1.h^-1 but it showed a significantly 50% increase at the dantrolene EC50 (t = 10.3, p < 0.0001) and lidocaine IC50 increased up to 35 ± 1.5 mM
Conclusions: Dantrolene relieves the inhibitory effect of lidocaine on medial pterygoid SERCA2a, suggesting that outer sarcoplasmic reticulum calcium is required for the inhibitory effect of the anesthetic. This finding might also break new ground in the treatment of local anesthetics-induced trismus.