Agonist-induced myopathy at the neuromuscular junction is mediated by calcium.

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Abstract
Inactivation of cholinesterases at mammalian neuromuscular junctions (nmj) produces extensive muscle necrosis. Fine-structurally, this myopathy begins near the nmj with an increase in large-diameter vesicles in the soleplasm, the dissolution of Z-disks, dilation of mitochondria, destruction of sarcoplasmic reticulum, and often a highly specific contracture of the muscle under the endplate. Since a Ca2+-activated protease which specifically removes Z-disks is known to exist in mammalian skeletal muscle, the myopathy after esterase inactivation may be due to the prolongation of acetylcholine lifetime and thus of Ca2+ influx. The myopathy was first produced near endplates by inactivating esterases with DFP followed by nerve stimulation for 1-2 h in vitro. The myopathy was later mimicked by bath application of carbamylcholine without esterase inhibitors. This myopathy could be prevented by inactivating the acetylcholine receptors (AChR) with .alpha.-bungarotoxin (.alpha.-BGT) or by removing Ca2+ from the bath with EGTA [ethylene glycol-bis-(.beta.-aminoethyl ether) N,N,N'',N''-tetraacetic acid]. Esterase inhibition leads to an agonist-induced myopathy, which is mediated by Ca2+ and requires an intact AChR.