Is excitation-contraction coupling impaired in myasthenia gravis?

Abstract

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 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.

• Authors: Miho 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
• Journal: Clinical 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
• PMID: 17307394 (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)