Download Slide 1 - AccessPharmacy

Glutamatergic neurotransmission. Glutamic oxaloacetic transaminase (GOT) converts α-ketoglutarate to glutamate in mitochondria. Glutamate also forms
from glutamine via mitochondrial glutaminase. Glutamate is transported into vesicles [6] by VGlut1 (or possibly other subtypes) for exocytotic release into
the synapse. Synaptic glutamate activates four main types of receptors. AMPA [2], kainate [3], and NMDA [4] receptors are cation channels. Membrane
depolarization in response to their activation causes neuronal excitation through cation influx. Metabotropic receptors (mGluR) [1,8] are coupled to G
proteins and are expressed on pre- and postsynaptic membranes. In addition, some mGluRs reside outside of the synapse. Postsynaptic mGluR excitation
in this example [1] results from preventing K+ efflux, but other mechanisms of excitation exist. Presynaptic mGluRs act to inhibit [8] glutamate (and other
Source: Biochemical and Molecular Basis, Goldfrank's Toxicologic Emergencies, 10e
neurotransmitter) release through modulating intracellular Ca2+ concentrations, as do presynaptic GABAB receptors in response to GABA binding [9].
Howland
M, Lewin
NA,
Nelson
LS, Goldfrank
LR. influx
Goldfrank's
Emergencies,
Available
at:
Figure 14–14Citation:
providesHoffman
a more RS,
detailed
illustration
of the
NMDA
receptor.
Excessive
of Ca2+Toxicologic
through NMDA
receptors10e;
(and2015
through
some AMPA
and
http://mhmedical.com/
Accessed:
August
03,
2017
2+
2+
kainate receptors) causes neuronal damage and cell death. A Mg ion normally blocks the NMDA receptor channel to prevent Ca influx despite
Copyright
© 2017depolarization
McGraw-Hill Education.
All rights
reserved
glutamate binding.
However,
of the neuronal
membrane
by cation influx resulting from activation of any of the other receptor types causes
2+
Mg to dissociate from the NMDA receptor and to allow potentially damaging inward Ca2+ currents in response to glutamate binding. Glutamate