Biomedical Engineering Reference
In-Depth Information
Chloride Ion Channels: Structure, Functions,
and Blockers
Satya P. Gupta and Preet K. Kaur
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310
2 Classification of Cl
Channels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
2.1 The CLC Chloride Channels . . ....................................................... 312
2.2 Cystic Fibrosis Transmembrane Conductance Regulator . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
2.3 Ca
2+
-Activated Chloride Channels (CaCC Channels) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
2.4 Ligand-Gated Cl
Channels . . . . . . .................................................... 317
2.5 Chloride Intracellular Channels (CLICs) ............................................ 319
2.6 Bestrophins ............................................................................ 321
3 Human Diseases Related to Chloride Ion Channels . . . .................................... 322
4 Chloride Ion Channel Blockers . . ........................................................... 322
4.1 Agents Acting at the Neuronal Chloride Channels
(GABA and Glycine Receptors) ...................................................... 323
4.2 Agents Acting with Chloride Channels in Muscle Cells . . . ......................... 324
4.3 Agents Acting on Epithelial Chloride Channels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
4.4 Agents Acting on Other Cl
Channels ............................................... 327
4.5 Other Cl
Transporting Systems and Their Blockers . .............................. 328
4.6 Mechanism of Action of Anionic Channel Blockers ................................ 329
5 Conclusion ................................................................................... 330
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
Abstract Chloride ion channels have been found to play crucial roles in the
development of human diseases, for example, mutations in the genes encoding
Cl
channels lead to a variety of deleterious diseases in muscle, kidney, bone, and
brain, including myotonia congenita, dystrophia myotonica, cystic fibrosis,
osteopetrosis, and epilepsy, and similarly their activation is supposed to be respon-
sible for the progression of glioma in the brain and the growth of malaria-parasite
in the red blood cells. Thus, the study of the structure, function, and blockers of
