Structure of Neuromuscular Junction

The structure of the neuromuscular junction explains why it is so powerful. An axonal branch terminates in a branched structure that is laden with mitochondria, synaptic vesicles, and a number of special features that ensure that when an action potential invades the terminal a sequence of events is set in motion, leading to the near-synchronous release of neurotransmitter as hundreds of synaptic vesicles fuse with the nerve’s plasma membrane and release their contents into the synaptic cleft. The main constituent of these synaptic vesicles is acetylcholine (ACh), the neurotransmitter at all skeletal muscle neuromuscular junctions. The released acetylcholine diffuses across the synaptic cleft, which is a mere 10 to 20 nm wide. It takes roughly 1 µsec for an ACh molecule to traverse the cleft and reach the synaptically specialized membrane of the muscle fiber, known as the postsynaptic membrane.

However, at least half of the released neurotransmitter never reaches the postsynaptic membrane because there is a high concentration of an enzyme on the cleft that enzymatically inactivates the neurotransmitter, cleaving it into acetate and choline. It may seem strange that this enzyme, known as acetylcholinesterase, should be juxtaposed between the nerve’s release site and the muscle fiber’s receptive site. However, the large amount of ACh released from hundreds of synaptic vesicles means that there is far more ACh available than is normally required to cause the muscle fiber to twitch when an electrical impulse from the axon invades the nerve terminal. This “safety factor” means that, in normal use, it is very unlikely that the available neurotransmitter will fail to cause the muscle to contract. The muscle contraction is initiated by the binding of ACh to the acetylcholine receptors (AChR) in the postsynaptic membrane. The AChRs are packed into the postsynaptic membrane at as high a concentration as their size permits, about 10,000 receptors per square micron of membrane, guaranteeing that any ACh molecule that makes it through this gauntlet of esterases will find a receptor.

The AChR is a typical ligand-gated ion channel. Thus, when ACh (the ligand) binds to the AChR, the receptor becomes an ion channel that allows cations to pass through a central pore. The main cations are sodium (Na⁺) and potassium (K⁺). The high concentration of Na⁺ outside and the negative resting membrane potential drives Na⁺ into the muscle fiber. The positive charges that enter the muscle fiber depolarize the muscle’s membrane potential from a negative value to a much less negative value. This depolarization initiates a muscle fiber action potential that propagates away from the NMJ in both directions, rapidly causing the muscle fiber to contract.