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Neuromuscular junction physiology in myasthenia gravis

Isoforms of the acetylcholine receptor in extraocular muscle and the contribution of sodium channels to the safety factor

From the Departments of Neurology (Drs. Kaminski and Ruff) and Neuroscience (Dr. Suarez), Case Western Reserve University School of Medicine, Cleveland Veterans Affairs Medical Center, University Hospitals of Cleveland, Cleveland, OH.
This work was supported by the Office of Research and Development, Medical Research Service of the Department of Veterans Affairs (Drs. Kaminski and Ruff). Dr. Kaminski was also supported by a National Institutes of Health grant (EY-00332). Dr. Ruff was also supported by the Muscular Dystrophy Association.
Address correspondence and reprint requests to Dr. Robert L. Ruff, Neurology Service 127(W), Cleveland VAMC, 10701 East Blvd., Cleveland, OH 44106.

Abstract.

Article abstract-The mammalian neuromuscular junction is a chemical synapse that uses acetylcholine as transmitter. Acetylcholine (ACh) is stored in the nerve terminal and is released from small membrane-bound vesicles that fuse with the nerve terminal membrane after depolarization of the nerve terminal. Calcium entry via P/Q-type calcium channels is necessary for transmitter release. The postsynaptic membrane of the muscle fiber has several unique properties that facilitate neuromuscular transmission. The postsynaptic membrane area is greatly expanded by synaptic folds. Acetylcholine receptors (AChR) are concentrated at the peaks of synaptic folds and sodium channels are concentrated in the troughs of the synaptic folds. The safety factor for neuromuscular transmission results from a combination of factors: the amount of ACh released, the high concentration of AChR, and the high concentration of sodium channels. AChR are firmly anchored in the membrane by a complex of proteins. The autoimmune attack in myasthenia gravis (MG) directed at acetylcholine receptors results in loss of postsynaptic membrane, AChR, and sodium channels. This article describes the different types of neuromuscular junctions on extraocular muscle fibers and their possible relevance to the susceptibility of extraocular muscle to MG.

NEUROLOGY 1997;48(Suppl 5): S8-S17

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