The Neuromuscular Junction (NMJ) is a specialized synapse that serves to transmit electrical impulses (action potentials) from the motor neuron nerve terminal to the skeletal muscle. Basically, the NMJ allows for efficient and reliable communication between the motor neuron nerve and the muscles required for contraction and movement. The primary chemical messenger in this synapse, which consists of the presynaptic region (containing the nerve terminal), the synaptic cleft and the postsynaptic surface, is acetylcholine. These regions are defined by the differential localization of specific proteins, which underlie their distinct anatomical features and their physiological roles.
Now it’s time to briefly sum up what goes on in the NMJ, as shown in the diagram above.
1. The action potential (or electrical impulse signal) reaches the nerve terminal in the presynaptic region. The hallmark feature of the nerve terminal is that it contains the synaptic vesicles, along with the proteins that help vesicle function. These vesicles are aligned near their release site, called an active zone.
2. When action potentials reach the nerve terminal they activate calcium channels, which open up and facilitate the influx of calcium into the presynaptic terminal, which in turn commences the process of vesicular release into the synaptic cleft.
3. The increase in intracellular calcium concentration triggers the fusion of the synaptic vesicles with the nerve terminal membrane. The mechanism of synaptic vesicle fusion involves conformational changes in multiple docking proteins both on the vesicle and the nerve terminal’s plasma membrane.
4. Once fused with the nerve terminal membrane, the vesicle releases its contents into the extracellular space, also known as the synaptic cleft. The chemical or neurotransmitters (in this case, acetylcholine) released then bind to their corresponding receptors on the postsynaptic surface (also known as the motor end plate in the NMJ).
5 & 6. Acetylcholine binds to its receptors and opens ligand-gated Na+/K+ channels. These structures are designed to optimize cholinergic neurotransmission in order to produce an end plate potential (EPP). The EPP is simply the net synaptic depolarization caused by the release of acetylcholine triggered by the nerve action potential. The EPP is a function of the miniature endplate potential (MEPP) amplitude, which represents the depolarization of the postsynaptic membrane produced by the contents of a single vesicle, and quantal content (number of transmitter vesicles released by a nerve terminal action potential. The EPP serves to open the voltage-gated Na+ channels in the postsynaptic region, which in turn results in an action potential that triggers muscle fiber contraction. These changes in the postsynaptic region potential result in muscle stimulation and contraction.
7. Acetylcholinesterase degrades acetylcholine so that it (choline) can be re-uptaked and recycled to produce new acetylcholine molecules. It’s activity terminates synaptic transmission.
Hughes, Benjamin W., et. al. 2006. Molecular architecture of the neuromuscular junction. Muscle & Nerve. 33(4): 445-461. DOI 10.1002/mus.20440
Motor Systems: Control of Movement and Behavior. 2008. Available at: http://www.colorado.edu/intphys/Class/IPHY3730/09motorsystems.html