Responses of intercostal muscle biopsies from normal subjects and patients with myasthenia gravis

Abstract

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.

Mechanisms of fatigue in normal intercostal muscle and muscle from patients with myasthenia gravis

“…42 Findings of the present study lend further support to reduced E-C coupling and contractility in muscles of MG patients. Such a defect in E-C coupling and contractility may be caused by some of the immunologic changes in MG patients.…”

Thymoma in Myasthenia Gravis: From Diagnosis to Treatment

“…There is also a rat model with thymoma and MG with RyR antibodies but no AChR antibodies, indicating that RyR antibodies may cause MG symptoms irrespective of AChR antibodies [25]. There are also several reports of excitation-contraction coupling defects in thymoma MG [26]. …”

Ryanodine receptor gene expression thymomas

“…11,12 Further, abnormalities of excitationcontraction coupling observed in some myasthenics would be consistent with RyR dysfunction, since the RyR functions as the calcium release channel of the sarcoplasmic reticulum. 11,12,14 The genesis of RyR antibodies is not known. Since RyR antibodies are not detected in nonthymoma-associated MG, immune damage of muscle is not a factor in generation of these antibodies.…”