Which neurotransmitter is released at the neuromuscular junction to initiate muscle contraction?

• A. Acetylcholine
• B. Dopamine
• C. Norepinephrine
• D. GABA

Answer: (A)

At the neuromuscular junction, the signal that starts muscle contraction is acetylcholine. When a motor neuron fires, calcium triggers acetylcholine-containing vesicles to fuse with the presynaptic membrane and release the transmitter into the synaptic cleft. Acetylcholine then binds to nicotinic receptors on the muscle’s motor end plate. These receptors are ligand-gated ion channels, so their opening lets sodium rush in (with some potassium going out), depolarizing the membrane and creating an end-plate potential. If this depolarization reaches threshold, an action potential travels along the muscle fiber, triggering calcium release from the sarcoplasmic reticulum and activating the contractile machinery.

The signal is rapidly terminated by acetylcholinesterase, which breaks down acetylcholine in the cleft, stopping the stimulus so the muscle can relax and be ready for the next impulse.

Other neurotransmitters listed—dopamine, norepinephrine, and GABA—play major roles in the CNS or autonomic control but are not the primary transmitters at the skeletal muscle neuromuscular junction.