Biomedical Engineering Reference
In-Depth Information
pentameric with 6
subunit isoforms [
90
]. On the contrary, the glycine
receptors have been found to be a pentameric assembly of ~48 kDa
a
,3
b
, and 3
g
a
1
subunit [
91
]
and 58 kDa
b
subunits [
92
]. To date, in humans
a
1
to
a
4
and
b
subunits have been
characterized.
2.4.2 Expression
GABA receptors are expressed in central as well as peripheral nervous systems,
while glycine receptors are prominently expressed in the spinal cord and the
medulla. They are also found in the retina [
93
], adrenal gland [
94
], kidney [
95
],
liver [
96
], and sperm [
97
]. GABA receptors are also found in nonneuronal tissue
where their function is not very clear. GABA and glycine receptors have been found
to often coexist in spinal cord neurons [
98
-
100
].
2.4.3 Functions
Both GABA and glycine receptors were found to be permeable to several ions in
the order SCN
>
F
with only a small difference that the former
are much more permeable to Cl
against F
than the latter. Further, the glycine
receptors have also been found to be permeable to NO
3
(
Br
>
Cl
>
I
) but not the GABA
receptors [
9
]. However, the GABA receptors have been shown to be additionally
permeable to HCO
3
with a permeability of ~20% of Cl
.
>
2.4.4 Disorders Associated
The disruption in GABA receptors has been found to produce epilepsy [
101
].
Recently, mutations in the
g
2
-subunit have been identified in patients suffering
from epilepsy [
102
,
103
]. However, not one but several disorders have been found
to be associated with mutations in glycine receptors, for example, hunching of
shoulders, flexure of arms, and clenching of fists [
9
].
2.5 Chloride Intracellular Channels (CLICs)
The CLICs are the proteins that function as intracellular chloride channels. The
term CLIC was derived from “Chloride Interacellular Channel” [
104
], and it was
proposed that CLICs were the first proteins to function as interacellular chloride
channels [
105
]. The first CLIC to be described was a 64 kDa protein (p64, now
known as CLIC5B) isolated by Landry et al. [
106
] from bovine kidney membrane
