The glutamatergic nerve terminal

Abstract

Glutamate as a neurotransmitterThe human brain has about lolo neurones, each of which, on average, makes about 1000 synaptic contacts with other neurones. Of these l O I 3 synapses perhaps up to 90% utilize amino acids as their neurotransmitter. Glutamate is the major excitatory amino acid (acting predominantly on depolarizing post-synaptic receptors) while 4-aminobutyrate (GABA) and glycine are the major inhibitory transmitters (acting on hyper-polarizing receptors). As well as playing the dominant role in fast information transfer, glutamate is of particular interest in view of its involvement in current models of memory and learning (Bliss and Dolphin, 1982;Cotman et al., 1988;Collingridge and Singer, 1990) and because a pathological release of glutamate in brain ischaemia is neurotoxic and a major contributor to the damage caused under these conditions (Rothman and Olney, 1986;Choi, 1988 ;Meldrum and Garthwaite, 1990).A synapse has a pre-synaptic element responsible for the storage and release of transmitter and a post-synaptic element containing one or more classes of receptor for the transmitter. The potent combination of electrophysiology and molecular cloning has allowed a dramatic advance in our understanding of post-synaptic events. Three classes of post-synaptic ionotropic (possessing an integral ion channel) glutamate receptors have been identified and cloned: the 2-amino-3hydroxy-5-methyl-4-isoxazole propionatekainate (AMPA/ KA) receptor Nakanishi et al., 1990;Sakmann, 1992), the high-affinity KA receptor (Egebjerg et al., 1991) and the N-methyl D-aSpartate (NMDA) receptor (Moriyoshi et al., 1991 ;Kumar et al., 1991 ;Barnard, 1992). Each can exist in many isoforms by combining subunits formed from distinct genes, by alternative splicing or by post-transcriptional modification (Monyer et al., 1991 ;Burnashev et al., 1992).The AMPNKA receptor is responsible for fast information transfer while the NMDA receptor is only operative when the post-synaptic membrane is independently depolarized by another receptor. This 'associative' behaviour of the latter is believed to underlie aspects of the learning process.

Partial inhibition of complex I activity increases Ca2+‐independent glutamate release rates from depolarized synaptosomes

“…The suggestion is that reduced ATP levels impede Na + /K + ATPase function resulting in a collapse of plasma membrane potential. Glutamate uptake is thought to occur with cotransport of three Na + in and one K + out thus relies on the maintenance of the ionic gradients across the membrane (Nicholls 1993). The results from resting synaptosomes (i.e.…”

Long-lasting inhibition of presynaptic metabolism and neurotransmitter release by protein S-nitrosylation

“…1A). The Ca 2+ -dependent component of the release represents vesicular neurotransmitter release, while Ca 2+ -independent release is most likely due to the reversal of membrane glutamate transporters [40]. To verify the vesicular nature of Ca 2+ -dependent release in our preparation, we performed two types of controls.…”

Modulation of the neuronal dopamine transporter activity by the metabotropic glutamate receptor mGluR5 in rat striatal synaptosomes through phosphorylation mediated processes

“…1990a , 1990b; Mount et al . 1990; Nicholls 1993), glutamate acting on diverse striatal receptors constitutes one of the potential modulators of DAT activity. The aim of the present study was to investigate the modulation of the neuronal DAT activity by mGluRs and to determine whether phosphorylation through diverse protein kinases was involved in this regulation.…”

“…2000). This preparation retains all the machinery required for the uptake of dopamine (Nicholls 1993).…”