Congenital canine myasthenia gravis: II. Acetylcholine receptor metabolism.

Abstract

Acetylcholine receptor (AChR) metabolism was studied in muscle from juvenile and adult dogs with congenital myasthenia gravis (CMG) and their unaffected littermates. Although the amount of AChR in the junctional region of innervated CMG muscle fibers was 25% of normal, or less, denervation of CMG fibers resulted in the appearance of AChR in extrajunctional membranes at as high a concentration as in denervated normal fibers. The rate of degradation of junctional AChR in CMG fibers explanted to organ culture did not differ significantly from normal. In monolayer cultures derived from enzyme-dissociated CMG muscle, myotubes of normal morphology developed, and the synthesis and degradation of AChR did not differ from normal. Addition of sera from dogs with the acquired autoimmune form of MG accelerated the degradation of AChR on cultured myotubes, but CMG dog sera were without effect. These data suggest that the low junctional membrane density of AChR in CMG does not reflect a primary inability of muscle to synthesize AChR, nor an accelerated degradation of AChR in the postsynaptic membrane, but rather a low insertion rate of AChR in the postsynaptic membrane.