MULTIPLE NEUROTRANSMITTER
SYNTHESIS, RELEASE, AND
SIGNALING FROM
INDIVIDUAL NEURONS
Many, perhaps most, nerve terminals co-localize and release multiple
neurotransmitters (NT), each presumably packaged in its own synaptic vesicles.
Major co-localized NTs, sorted by transmitter and by fiber type, are presented
in the table.
Some authors have noted as many as seven or more NTs present in a
single type of nerve terminal. It should be noted that some NTs are present in
the presynaptic cytoplasm and are not released by quantal (vesicle-based)
release. Some NTs are packaged in vesicles in the cell body and transported by
axonal transport (e.g., neuropeptides), while other NTs are synthesized and/or
packaged locally in the nerve terminals (e.g., amino acids,
monoamines).
NT release is usually nonlinear, with some NTs
diminishing their quantal release at higher action potential (AP) frequencies,
while other co-localized NTs (especially some neuropeptides) are released only
at much higher AP frequencies. A further phenomenon affecting the functional
consequence of NT release is the frequent NT-receptor mismatch. Some NTs are
released into a synaptic cleft and immediately activate receptors on the
postsynaptic site (e.g., ACh at the neuromuscular junction). However, some NTs,
when released, have no local receptors with which to interact, except at
distant sites. Hence, NT-receptor activation in these circumstances may occur
only during particularly robust or prolonged NT transmitter release.
