Modulation of fast synaptic transmission by presynaptic ligand-gated cation channels

There is now considerable evidence demonstrating that ligand-gated cation channels (i.e., P2X, nicotinic, kainate, NMDA, AMPA and 5-HT₃ receptors), in addition to mediating fast excitatory neurotransmission, may be located presynaptically on nerve terminals in the peripheral and central nervous systems where they function to modulate neurotransmitter release. This modulation can be facilitation, inhibition or both. In this article, we first outline the multiple mechanisms by which activation of presynaptic ligand-gated cation channels can modulate spontaneous and evoked neurotransmitter release, before reviewing in detail published electrophysiological studies of presynaptic P2X, nicotinic, kainate, NMDA, AMPA and 5-HT₃ receptors.