The neuromuscular junction is an anatomic location in which signals are transmitted from a motor neuron to a muscle fiber via neurotransmitters (acetylcholine) which diffuse across a synapse. These signals cause muscle contraction.
The neuromuscular junction consists of several components that allow for transmission of signals from the motor neuron to motor end plate. The motor neuron is made up of a cell body that has dendritic branches and contains a nucleus. The cell body connects to a myelin-covered axon composed of Schwann cells, which allows for faster impulse conduction. As the axon ends, it becomes the axon terminal that branches into processes. Each axonal process has a prejunctional motor nerve ending that innervates one muscle fiber. Mitochondria, voltage-gated calcium channels, and presynaptic vesicles containing acetylcholine reside in the motor nerve ending.
The synaptic cleft of the neuromuscular junction is the area 30-50 nm wide that connects the basement membranes of the prejunctional motor nerve ending and the postjunctional muscle fiber. This cleft is a chemical synapse in which neurotransmitters, specifically acetylcholine, are released from the motor nerve ending to attach to receptors on the postjunctional muscle fiber.
The postjunctional membrane of the muscle fiber consists of junctional folds that maximize surface area (Figure 124-1). Here, nicotinic acetylcholine receptors (sodium channels) as well as voltage-gated calcium channels reside. When an action potential travels along the axon and depolarizes the presynaptic/prejunctional nerve ending, acetylcholine is released and diffuses across the synaptic cleft. Once acetylcholine binds the acetylcholine receptors it causes an action potential in the muscle fiber, resulting in muscle movement.
Neuromuscular junction. (Reproduced with permission from Barrett KE, Barman SM, Boltano S, Brooks HL. Ganong’s Review of Medical Physiology, 24th ed. McGraw-Hill Companies, Inc. All rights reserved.)
ACETYLCHOLINE AND ACETYLCHOLINE RECEPTORS
Acetylcholine was the first neurotransmitter discovered. It is highly involved in transmission of signals in the parasympathetic and sympathetic nervous systems as well as at the neuromuscular junction. Acetylcholine binds acetylcholine receptors, which can be classified as either nicotinic or muscarinic receptors. At the neuromuscular junction, acetylcholine binds to nicotinic receptors. The receptor consists of five subunits (two alpha subunits and a single beta, gamma, and delta subunit) that form a channel, allowing ion flow.
Acetylcholine is only capable of binding the alpha subunits. Acetylcholine must occupy both alpha subunit sites for a conformational change to occur, which then leads to an action potential. Acetylcholine is broken down into acetate and choline by acetylcholinesterase. This process occurs via hydrolysis. Acetylcholinesterase is located at the motor end plate adjacent to the acetylcholine receptors. The choline undergoes reuptake by the presynaptic nerve cell and, together with acetyl-CoA, acetylcholine is synthesized and stored into vesicles.