Biomedical Engineering Reference
In-Depth Information
3 Human Diseases Related to Chloride Ion Channels
The mutations in Cl
channels have been found to be responsible for the develop-
ment of a number of deleterious diseases in muscle, kidney, bone, and brain,
including myotonia congenita, dystrophia, cystic fibrosis, osteopetrosis, and epi-
lepsy. Not only the mutations, but activation also of these channels has been
responsible for the development of certain diseases, such as the progression of
glioma in the brain and the growth of the malaria parasite in the red blood cells
[
120
-
123
]. In addition, it has also been found that a loss of Cl
channel activity
may also mediate the development of chronic pancreatitis, bronchiectasis, congen-
ital bilateral aplasia of vas deferens, alcoholism, cataract, and Best's disease [
3
].
The development of the various forms of cystic fibrosis (CF) and Bartter syndrome
has been attributed to the defective Cl
transport in epithelial cells [
124
]. Mutations
in
-1 subunit of inhibitory glycine receptor have been found to cause the dominant
neurological disorder, hyperekplexia [
125
-
128
]. All such human diseases thus
known to be associated with the abnormality in Cl
channels have been well
described by Puljak and Kilic [
3
]. They can be briefly mentioned here as follows.
ClC-1: Myotonia congenita Becker [
36
], myotonia congenita Thomsen [
129
],
dystrophia myotonica 1 [
130
,
131
], and dystrophia myotonica 2 [
130
,
132
]
ClC-2: Childhood absence epilepsy type 3, juvenile absence epilepsy, juvenile
myoclonic epilepsy, and epilepsy with grand mal [
133
], and seizures on awakening
ClC-Kb: Bartter syndrome III [
40
]
ClC-Ka, ClC-Kb (Barttin): Bartter syndrome IV or BSND [
134
,
135
]
ClC-5: Dent's disease [
136
-
138
]
ClC-7: Autosomal dominant osteopetrosis [
139
] and autosomal recessive
osteopetrosis [
140
]
CFTR: Cystic fibrosis [
141
], idiopathic chronic pancreatitis [
142
-
144
], bronchi-
ectasis [
145
-
148
], and congenital bilateral absence of vas deferens [
149
-
152
]
Bestrophin: Best's disease [
153
-
155
], adult-onset vitelliform [
156
], macular and
concentric annular macular dystrophy [
156
]
Unknown: Cataract [
157
-
160
]
GABA
A
: Juvenile myoclonic epilepsy [
161
], childhood absence epilepsy type
2[
103
], generalized epilepsy with febrile seizures plus severe myoclonic epilepsy
in infancy [
162
], alcoholism [
163
,
164
], and insomnia [
165
]
GlyR: Hereditary hyperekplexia [
125
-
128
]
Association of these diseases with Cl
channels suggests that these channels may
be novel targets for the development of useful drugs for a broad spectrum of diseases.
a
4 Chloride Ion Channel Blockers
The Cl
channels are usually present in the neurons and muscle cells and in
epithelial cells. While in neurons and muscle cells they regulate the excitability,
in the epithelial cells they mediate the transepithelial transport of salt and water.
