nmj

The neuromuscular junction (NMJ) is the chemical synapse between a lower motor neuron and a skeletal muscle fiber in the peripheral nervous system. It translates neuronal action potentials into muscle contraction, coordinating voluntary movement and reflexes. The NMJ consists of a presynaptic motor nerve terminal, a specialized postsynaptic muscle membrane called the motor endplate, and the synaptic cleft that contains the basal lamina.

In the presynaptic terminal, action potentials trigger the opening of voltage-gated calcium channels, causing synaptic vesicles containing acetylcholine (ACh) to fuse with the membrane and release ACh into the cleft. The postsynaptic membrane at the motor endplate displays densely packed junctional folds rich in nicotinic acetylcholine receptors (nAChRs). Acetylcholinesterase in the synaptic basal lamina rapidly hydrolyzes ACh, terminating the signal. Activation of nAChRs by ACh causes an inward cation current, producing a large end-plate potential that, if sufficient, triggers a muscle action potential and subsequent contraction.

Following contraction, calcium ion homeostasis is restored via pumps in the sarcoplasmic reticulum, and the muscle relaxes. The NMJ features precise molecular organization that includes agrin–MuSK–Lrp4 signaling, which clusters ACh receptors at the endplate, and a specialized basal lamina that supports synaptic transmission.

Clinical relevance includes disorders of NMJ transmission such as myasthenia gravis, Lambert-Eaton myasthenic syndrome, and congenital myasthenic syndromes, as well as acquired conditions or toxins that affect ACh release or receptor function. Diagnosis commonly uses electrophysiological tests like repetitive nerve stimulation and single-fiber EMG, while treatment focuses on enhancing transmission or modulating the immune response.