Succinylcholine metabolite succinic acid alters steady state activation inmuscle sodium channels

Background: Animal experiments revealed that succinylcholine produced masse ter muscle rigidity and activated myotonic discharges despite neuromuscular blockade with a nondepolarizing blocker. These results suggest that either succinylcholine or its metabolites might interfere directly with voltage-o perated ion channels of the sarcolemma, The aim of this study was to examin e effects of one product of succinylcholine hydrolysis, succinic acid, on v oltage-gated muscle sodium (Na+) channels. Methods: Alpha subunits of human muscle sodium channels were heterologously expressed in HEK293 cells. Activation of Na+ currents was examined applyin g standard whole-cell voltage-clamp protocols in the absence (control and w ashout) and presence of succinic acid in different concentrations (0.05-10 mM), Results: Succinic acid shifted the midpoints of steady state activation plo ts In the direction of more negative test potentials, indicating that chann els open during smaller depolarizations in the presence of the drug. The ma ximum amount of the negative shift in 10 mM succinic acid was -6.3 +/- 1.7 mV; the EC50 for this effect was 0.39 mM, In addition, succinic acid (10 mM ) significantly enhanced maximum currents after depolarizations with respec t to a series of control experiments. Conclusion: Succinic acid facilitates voltage-dependent activation in muscl e sodium channels in vitro. This might lead to muscle hyperexcitability in vivo.