Structural determinants of the reliability of synaptic transmission at the vertebrate neuromuscular junction.
The reliability of neuromuscular transmission depends on the size and molecular organization of the neuromuscular junction. Comparative studies show that the quantal release per unit area is similar at neuromuscular junctions in a number of species in spite of wide variation in synaptic area. They also show an inverse relationship between the size of the nerve terminal and the extent of postsynaptic folding. Evidence is presented supporting the view that the folds, and the voltage-gated sodium channels present in them, effectively amplify synaptic currents. How are the size and molecular organization of the neuromuscular junction determined? Studies with botulinum toxin, including our new work on humans, reveal striking "adaptive plasticity" of the nerve terminal. However, the links between synaptic size and effective transmission remain unclear. On the postsynaptic side, we have shown that mRNA encoding sodium channels is concentrated at the adult junction. During development, mRNA accumulates just before the protein it encodes. Throughout development the sodium channels are associated with ankyrinG and both proteins are initially excluded from the junctional acetylcholine receptor cluster, possibly accounting for the formation of the boundary between the domains occupied by the two key postsynaptic ion channels. These findings have important clinical implications. Reduced transmitter release may result from small nerve terminals as much as from defective release. Abnormal folding is likely to reduce the reliability of transmission. A better understanding of how the structural features that influence the reliability of the neuromuscular transmission are controlled should be of general interest to neuroscientists and of use to clinicians.
Slater
Clarke R
CR
School of Neurology, Neurobiology and Psychiatry, Faculty of Medical Sciences, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. c.r.slater@ncl.ac.uk
D000818:Animals; D006801:Humans; D018482:Muscle, Skeletal / Q000502:physiology / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000502:physiology* / Q000648:ultrastructure*; D009435:Synaptic Transmission / Q000502:physiology*