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Is excitation-contraction coupling impaired in myasthenia gravis?

AbstractOBJECTIVE:
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 Ca(2+) 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.
AuthorsMiho Nakata, Satoshi Kuwabara, Naoki Kawaguchi, Hirokatsu Takahashi, Sonoko Misawa, Kazuaki Kanai, Noriko Tamura, Setsu Sawai, Masakatsu Motomura, Hirokazu Shiraishi, Masaharu Takamori, Takahiro Maruta, Hiroaki Yoshikawa, Takamichi Hattori
JournalClinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology (Clin Neurophysiol) Vol. 118 Issue 5 Pg. 1144-8 (May 2007) ISSN: 1388-2457 [Print] Netherlands
PMID17307394 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Immunosuppressive Agents
  • Receptors, Cholinergic
  • Ryanodine Receptor Calcium Release Channel
  • Protein-Tyrosine Kinases
  • Tacrolimus
Topics
  • Action Potentials (physiology)
  • Adult
  • Aged
  • Electric Stimulation
  • Electromyography
  • Female
  • Humans
  • Immunohistochemistry
  • Immunosuppressive Agents (pharmacology)
  • Intercostal Muscles (physiopathology)
  • Male
  • Middle Aged
  • Muscle Contraction (physiology)
  • Muscle, Skeletal (physiopathology)
  • Myasthenia Gravis (complications, physiopathology)
  • Protein-Tyrosine Kinases (metabolism)
  • Receptors, Cholinergic (metabolism)
  • Ryanodine Receptor Calcium Release Channel (metabolism)
  • Tacrolimus (pharmacology)
  • Thymoma (complications, physiopathology)
  • Thymus Neoplasms (complications, physiopathology)

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