Responses of intercostal muscle biopsies from normal subjects and patients with myasthenia gravis.
In order to evaluate the mechanisms of weakness in muscles of patients with myasthenia gravis (MG), intercostal muscle biopsies were obtained from 9 normal subjects and 6 MG patients, and the compound muscle action potential (AP) and tension responses to nerve and muscle stimulation, and contracture responses on exposure to caffeine, were monitored in vitro. In normal muscle, on stimulation of the nerve or muscle at 30 to 100 Hz, the AP responses showed decrement in amplitude, one-third of which was attributable to failure of neuromuscular transmission and two-thirds to failure of muscle membrane excitation. On stimulation at 1 to 5 Hz, the AP responses showed very little decrement, while the contractile responses showed significant fade in tension, due to failure of E-C coupling or contractility. In muscle from patients with generalized MG, stimulation of the nerve at all frequencies (1 to 100 Hz) caused much greater decrement in APs and fade in tension responses than in normal muscle, due mainly to failure of neuromuscular transmission. However, at 100 Hz, 40% of the decrement in APs was due to failure of muscle membrane excitation, and at 1 to 5 Hz, 40% of the fade in tension was due to failure of E-C coupling or contractility, as in normal muscle. On direct stimulation the contraction and half-relaxation times were slower and the tetanic tension was smaller than in normal muscle, especially in the MG patient with thymoma. Caffeine-induced contractures were smaller in MG muscle than in normal muscle. These results indicate that while the weakness of MG muscle is due mainly to failure of neuromuscular transmission, it is also partly due to reduced E-C coupling or contractility.
Pagala
M K
MK
Department of Medicine, Maimonides Medical Center, Brooklyn, NY 11219.
Nandakumar
N V
NV
Venkatachari
S A
SA
Ravindran
K
K
Namba
T
T
Grob
D
D
D000200:Action Potentials; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000328:Adult; D000368:Aged; D001706:Biopsy; D002110:Caffeine / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D004576:Electromyography; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D066298:In Vitro Techniques; D007366:Intercostal Muscles / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D007367:Intercostal Nerves / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009157:Myasthenia Gravis / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*
D002110:Caffeine; D000251:Adenosine Triphosphatases