Early Postdenervation Depolarization Is Controlled by Acetylcholine and Glutamate via Nitric Oxide Regulation of the Chloride Transporter

Resting non-quantal acetylcholine (ACh) and probably glutamate (Glu) release from nerve endings activates M1- and NMDA receptor-mediated Ca²⁺ entry into the sarcoplasm with following activation of NOS and production of NO. This is a trophic message from motoneurons, which keeps the Cl^– transport inactive in the innervated sarcolemma. After denervation, the secretion of ACh and Glu at the neuromuscular junction is eliminated within 3–4 h and the production of NO in the sarcoplasm is lowered. As a result, the Cl^– influx is probably activated by dephosphorylation of the Cl^– transporter with subsequent elevation of intracellular Cl^– concentration. The equilibrium Cl^– potential becomes more positive and the muscle membrane becomes depolarized.