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.