Possible role of 18-kDa translocator protein (TSPO) in etifoxine-induced reduction of direct twitch responses in isolated rat nerve-skeletal muscle preparations
Purpose: To determine the effects of etifoxine on directly-elicited twitch tension of isolated rat nerveskeletal muscle preparations and to propose a possible explanation of the mechanism of the observed effect.
Methods: Striated muscles contractile activity was elicited by electrical field stimulation. The effects of etifoxine and nifedipine on direct single twitch response were studied.
Results: The results demonstrate that the effect of etifoxine on skeletal muscle depends on the concentrations: low concentrations (10-8 М and 10-7 М) have little effect on twitch tension, whereas higher concentrations (10-6 М and 10-5 М) induced a significant decrease in the direct single twitch response in comparison to controls. The mean IC50 (reduction of directly-elicited twitch tension) of etifoxine was 0.85 x 10-6 M. The selective L-type calcium channel blocker nifedipine (10-5 М) induced a greater decrease in the muscle force than 10-6 М etifoxine. The different abilities of etifoxine and nifedipine to reduce direct single twitch response may be related to their distinct mechanisms of action. The observed effect of etifoxine could be more complex. Probably etifoxine acts as a non-selective agent not only on L-type calcium channels Cav1.1 localized in sarcolemma but also on 18-kDa translocator protein (TSPO) in skeletal muscle.
Conclusion: Etifoxine-induced reduction of direct twitch responses could be attributed to an effect on TSPO and Cav1.1. Knowledge of the effects of TSPO ligands on the contraction of skeletal muscle might explain the role of TSPO in muscle contractility.
Keywords: Etifoxine, TSPO, Calcium channels, Direct single twitch response, Striated muscle