Succinylcholine metabolite succinic acid alters steady state activation in muscle sodium channels.
BACKGROUND
Animal experiments revealed that succinylcholine produced masseter 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-operated ion channels of the sarcolemma. The aim of this study was to examine effects of one product of succinylcholine hydrolysis, succinic acid, on voltage-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 applying standard whole-cell voltage-clamp protocols in the absence (control and washout) and presence of succinic acid in different concentrations (0.05-10 mm).


RESULTS
Succinic acid shifted the midpoints of steady state activation plots in the direction of more negative test potentials, indicating that channels open during smaller depolarizations in the presence of the drug. The maximum 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 respect to a series of control experiments.


CONCLUSIONS
Succinic acid facilitates voltage-dependent activation in muscle sodium channels in vitro. This might lead to muscle hyperexcitability in vivo.
Haeseler
G
G
Department of Anesthesiology, Hannover Medical School, Hannover, Germany. Haeseler.Gertrud@MH-Hannover.de
Petzold
J
J
Hecker
H
H
Würz
A
A
Dengler
R
R
Piepenbrock
S
S
Leuwer
M
M
D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004558:Electric Stimulation; D006801:Humans; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000187:drug effects*; D019802:Succinic Acid / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D009467:Neuromuscular Depolarizing Agents; D015222:Sodium Channels; D019802:Succinic Acid