Neuromuscular Junction

Abstract

The neuromuscular junction (NMJ) is the site of communication between motor nerve axons and muscle fibres. It is composed of four specialised cell types: motor neurons, Schwann cells, muscle fibres and the recently discovered kranocytes. The function of the NMJ is to transmit signals from the motor neuron to the skeletal muscle fibre quickly and reliably, to ensure precise control of skeletal muscle contraction and therefore voluntary movement. The reliability of transmission is aided by specialised architecture (multiple active zones, junctional folds) that promotes high levels of transmitter release, large and reliable postsynaptic responses to transmitter binding and rapid termination of signalling events. In the last century, the structure and function of the NMJ has been extensively studied, which has been instrumental in uncovering many of the fundamental processes of chemical synaptic transmission. Key Concepts: The somatic neuromuscular junction is the site of communication between motor neurons and skeletal muscle fibres. Specialisations of the neuromuscular junction mean that activity in and release of transmitter from motor neurons produces contraction of skeletal muscle fibres rapidly and reliably. The neuromuscular junction comprises four cell types: the motor neuron, terminal Schwann cell, skeletal muscle fibre and kranocyte, with the motor neuron and muscle fibre separated by a gap called the synaptic cleft. The motor nerve terminal contains synaptic vesicles, filled with neurotransmitter, which release their transmitter into the synaptic cleft at multiple specialised sites called active zones, in response to action potential firing. Released transmitter acts at receptors on the muscle membrane, which occur in high‐density clusters at the peaks of muscle membrane infoldings called junctional folds. Junctional folds are unique to the neuromuscular junction, increasing the reliability of transmission by localisation of acetylcholine receptors to the crests of the folds and enhancing the effect of depolarisation by localisation of sodium channels in the troughs. Schwann cells are essential for the development and maintenance of the neuromuscular junction and play important roles in the remodelling and regeneration of damaged neuromuscular junctions. Acetylcholinesterase in the synaptic cleft hydrolyses acetylcholine and limits the temporal and spatial effects of released of acetylcholine, ensuring precision of muscle control. Transmitter binding causes two types of electrical signals in skeletal muscle, miniature endplate potentials caused by the spontaneous release of a single vesicle of acetylcholine and larger endplate potentials. Endplate potentials are caused by activity‐dependent release of multiple transmitter‐filled vesicles and trigger action potential firing in, and thus contraction of, the muscle fibre. The neuromuscular junction is an accessible and relatively easy to study synapse that has led to tremendous progress in our understanding of synapses and in particular neurotransmitter release and continues to be a useful experimental model and educational tool.

A Novel Bioengineered Functional Motor Unit Platform to Study Neuromuscular Interaction

“…Furthermore, it has also been demonstrated that denervated myotubes within a nerve-muscle co-culture system fail to exhibit contractile function or characteristics of mature development; they eventually deteriorate, despite the elevated concentration of nerve-derived secretions in the culture environment [ 50 ]. Interestingly, the myotubes in our co-culture model initiated spontaneous contractions as early as 72 h post co-culture [ 27 ], suggesting the initial emergence of NMJ formation, due to the myotube requirement for nervous input from the motor neurons to induce contraction [ 51 ]. When compared to aneural in vitro SkMC cultures, the benefits of our co-culture system are apparent, as co-cultured myotubes exhibit advanced stages of differentiation that monocultures of SkMCs fail to achieve.…”

Heterochronic neuromuscular junction development in an Australian marsupial (Macropus fuliginosus)

“…Subsequent binding of ACh by postsynaptic acetylcholine receptors (AChRs) in the plasma membrane of the muscle cell triggers muscle contraction. The ease of accessibility and comparative simplicity of the somatic NMJ have placed it at the forefront of discoveries about chemical synaptic transmission for over a century (Hong & Etherington, ).…”