Is excitation-contraction coupling impaired in myasthenia gravis?

Objective: To investigate whether excitation-contraction (E-C) coupling of muscle is impaired in patients with myasthenia gravis (MG). Methods: In 51 patients with generalized MG and 35 normal subjects, compound muscle action potentials (CMAPs) of the abductor pollicis brevis, and movement-related potentials using an accelerometer placed at the thumb tip were simultaneously recorded after median nerve stimulation at the wrist. The E-C coupling time (ECCT) was estimated by a latency difference between CMAP and movement-related potential. Antibodies against acetylcholine receptor (AChR), ryanodine receptor (RyR), and muscle specific receptor tyrosine kinase (MuSK) were measured by immunoassays. Results: The mean ECCT was significantly longer in patients with MG (mean SEM; 2.79 +/- 0.1 ms; p = 0.002) than in normal controls (2.52 +/- 0.1 ms). Among MG patients, the mean ECCT was longer for patients with thymoma than for those without it (P = 0.04), and was shorter for patients treated with FK506 (an immunosuppressant and also an enhancer of RyR related Ca2+ release) than for those not receiving this treatment (p = 0.04). ECCT had no significant correlation with anti-AChR, anti-RyR, or anti-MuSK antibodies. Conclusions: In MG, E-C coupling appears to be impaired, particularly in patients with thymoma, and FK506 possibly facilitates E-C coupling. Significance: The functional implication of impaired E-C coupling is not established, but it may contribute to muscle weakness in patients with MG. (c) 2007 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.