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 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.


CONCLUSIONS
The functional implication of impaired E-C coupling is not established, but it may contribute to muscle weakness in patients with MG.
Nakata
Miho
M
Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
Kuwabara
Satoshi
S
Kawaguchi
Naoki
N
Takahashi
Hirokatsu
H
Misawa
Sonoko
S
Kanai
Kazuaki
K
Tamura
Noriko
N
Sawai
Setsu
S
Motomura
Masakatsu
M
Shiraishi
Hirokazu
H
Takamori
Masaharu
M
Maruta
Takahiro
T
Yoshikawa
Hiroaki
H
Hattori
Takamichi
T
D000200:Action Potentials / Q000502:physiology; D000328:Adult; D000368:Aged; D004558:Electric Stimulation; D004576:Electromyography; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007366:Intercostal Muscles / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009157:Myasthenia Gravis / Q000150:complications / Q000503:physiopathology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology; D013945:Thymoma / Q000150:complications / Q000503:physiopathology; D013953:Thymus Neoplasms / Q000150:complications / Q000503:physiopathology
D007166:Immunosuppressive Agents; D011950:Receptors, Cholinergic; D019837:Ryanodine Receptor Calcium Release Channel; D011505:Protein-Tyrosine Kinases; D016559:Tacrolimus