Biomedical Engineering Reference
In-Depth Information
homology with members of omega GST superfamily. Unlike other ion channels,
they exist in dimorphic form: either a soluble globular protein, or as an integral
membrane protein suggested to form functional ion channels. Bestrophins are
a group of four proteins, which have been found to support Cl
channel activity.
The first member of this family, bestrophin 1, is relatively well studied and has been
shown to support Ca
2+
-activated chloride current in the basal membrane of the
retinal pigment epithelium. There is no evidence that it itself functions as a chloride
ion channel. It is assumed to primarily reside in epithelium reticulum and not in the
plasma membrane.
Number of diseases have been found to be related to the abnormality of Cl
channels, for example, the mutations in them lead to several deleterious diseases in
muscle, kidney, bone, and brain, including mytonia congenita, dystrophia, cystic
fibrosis, osteopetrosis, and epilepsy, their activation may lead to progression of
glioma in the brain and the growth of malaria parasite in the red blood cells, and the
loss of their activity may mediate the development of chronic pancreatitis, bronchi-
ectasis, congenital bilateral aplasia of vas deferens, alcoholism, cataract, and Best's
disease. Thus, the blockers of Cl
channels may be developed as useful therapeutic
agents against many of these diseases. So far there are drugs such as picrotoxin,
a mixture of picrotoxinin (1) and picrotin (2), acting as blocker of GABA receptor,
and cyanotriphenylborate (5) acting as the blocker of glycine receptors. Some
polycyclics, benzoates, phenoxyacetates, and sulfonates and sulfonamides have
been found to block Cl
channels in muscle cells, and broad range of anionic
ions such as diphenylamine carboxylate (10), gluconate (11), and glibenclamide
(12), have been found to block CFTR channel in epithelial cells. Disulfonic stilbene
DIDS has been found to potentially block the CaCC in mammalian cells, and
indanylooxyacetic acid (17) is a potential blocker of CLIC channels.
Thus, this article presents all important aspects of Cl
channels, which may help
the medicinal chemists to develop important drugs for many diseases.
References
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