The Neuromuscular Junction

A neuromuscular junction (NMJ) is the synapse or junction of the axon terminal of a motor neuron with muscle fibre plasma membrane [1]. Motor neurons are required for the coordinated contraction of skeletal muscles. In mature muscle, motor axon terminals are located in deep and regular invaginations of the muscle plasma membrane termed postjunctional folds [2]. Acetylcholine receptors (AChRs) are concentrated at the crests of these postjunctional folds. The nerve terminal contains synaptic vesicles (SVs), each of which contains 5000 to 10000 molecules of acetylcholine (ACh) [1]. An action potential at the nerve terminal results in the opening of voltage-gated calcium channels. The ensuing increase in cytosolic Ca2+ initiates a train of events which result in the fusing of the SVs with the nerve terminal plasma membrane and the release of ACh into the synaptic cleft [1]. AChR is a transmembrane ligand gated cation channel consisting of five subunits arranged as a pentameric unit. The channel pore opens in response to the binding of two ACh molecules. This allows sodium to enter and depolarize the muscle cell membrane, which initiates the propagation of action potentials across the surface of the muscle, which through a number of steps results in muscle contraction [1]. In vertebrates the site of junction formation is not predetermined [3]. Functional synapses form within minutes to hours after contact between developing motor neurons and myotubes. However, in mammals, fully differentiated NMJs require several weeks after the first contacts are made to mature [3].

Refs

  1. Hirsch, N.P. 2007. Neuromuscular junction in health and disease. British Journal of Anaesthesia. 99:132-138.
  2. Burden, S.J. 2002. Building the Vertebrate Neuromuscular Synapse. J Neurobiol. 53:501–511.
  3. Burden, S.J. 1998. The formation of neuromuscular synapses. Genes & Dev. 12:133-148.
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