Biomedical Engineering Reference
In-Depth Information
NR1
NR2A
NR2B
NR2C
NR2D
NR3A
NR3B
GluR1
GluR4
GluR2
GluR3
GluR7
GluR6
GluR5
NMDA
AMPA
Kainic
acid
KA1
KA2
mGluR1
mGluR5
mGluR2
mGluR3
mGluR6
mGluR7
mGluR8
mGluR4
Group I
Group II
Group III
20
40
60
80
100
Percent amino acid identity
FIGURE 12.1
Phylogenetic tree showing the amino acid sequence identity between cloned mammalian glu-
tamate receptors. The subgroups according to receptor pharmacology have been noted. The NMDA, AMPA,
and kainic acid receptors belong to the superfamily of ligand-gated ion channels whereas the metabotropic
glutamate receptors (mGluR1-8) belong to the superfamily of GPCRs.
The same signaling molecule can act on both G protein-coupled receptors (GPCRs) and ligand-gated
ion channels (Figure 12.1). One of the reasons for the heterogeneity is that it allows cells to be regulated
in subtle ways. For example, whereas the fast synaptic action potential is initiated by glutamate receptors
of the ligand-gated ion channel family, these receptors are themselves regulated by slower and longer
acting glutamate receptors from the GPCR family. The action on these two receptor families is shared
by a number of other neurotransmitters such as gamma-aminobutyric acid (GABA) (Chapter 15),
acetylcholine (Chapter 16), and serotonin (Chapter 18).
12.1.1 S
YNAPTIC
P
ROCESSES
AND
M
ECHANISMS
Receptors are located in a complex, integrated, and highly interactive environment, which can be
further illustrated by the processes and mechanisms of synapses (Figure 12.2). The synapses are key
elements in the interneuronal communication in the peripheral and in the central nervous system
(CNS). In the CNS, each neuron has been estimated to have synaptic contact with several thousand
other neurons, making the structure and function of the CNS extremely complex.
The receptor is activated upon release of the signaling molecule and it is, evidently, equally
important to stop the signaling again. This is often achieved by transporters situated in the vicinity
