Presynaptic ionotropic receptors and control of transmitter release

Neurotransmission at many central synapses can be regulated by various presynaptic ionotropic receptors. The regulatory mechanism depends on the properties of the receptor, as well as on the characteristics of the specific synapse.Anionic and Ca2+-impermeable cationic receptors modulate release by affecting the presynaptic membrane potential. They can shunt action potential propagation to inhibit release, or bring membrane potential closer to threshold to enhance release.Ca2+-permeable receptors can modulate release by altering the intraterminal concentration of Ca2+. They can do so in three different ways: by bringing membrane potential closer to the activation threshold of Ca2+ channels, by directly allowing Ca2+ entry, and by promoting Ca2+-dependent Ca2+ release from internal pools.Not all the actions of presynaptic ionotropic receptors depend directly on ion flow. Kainate and NMDA (N-methyl-D-aspartate) receptors can modulate release through a metabotropic effect and through the production of nitric oxide, respectively.There are several possible sources of endogenous agonist to activate presynaptic ionotropic receptors. They include glia, dendrites and axons. In addition, axonal release can act on presynaptic receptors present in a neighbouring synapse or on autoreceptors to modulate its own release.To be more informative, future studies of presynaptic modulation should aim to take into account the physiological context in which such a modulation might take place.