Trans-synaptic homeostasis at the myasthenic neuromuscular junction.

Abstract

Properly sustained impulse transmission at the neuromuscular junction (NMJ) is crucial for successful muscle contraction. To guarantee this, NMJs not only possess a considerable safety factor in transmission but also have the ability to adjust the presynaptic acetylcholine release level to cope with any changes in the postsynaptic neurotransmitter sensitivity. This review will provide overview on the discovery and characterization of this synaptic homeostatic mechanism, especially in the condition of the neuromuscular disorder myasthenia gravis (MG) where the postsynaptic transmitter sensitivity at the NMJ becomes severely reduced due to autoimmune attack of acetylcholine receptors. Because homeostatic signalling and adaptation is presumably maximally active in this condition, NMJs from MG animal models are important study objects. Although candidate post- and presynaptic factors as well as the retrograde signals have been proposed, the homeostatic mechanism at the MG NMJ is still incompletely understood. Further identification and functional characterization of key factors is important because these may form new therapeutic targets in MG.