Disorders of membrane channels or channelopathies

Objective: To review the structure and function of membrane ion channels wi th special emphasis on inherited nervous system channel disorders or channe lopathies. Results: Channels are pores in the cell membrane. Through these pores ions flow across the membrane and depolarize or hyperpolarize the cell. Channels can be classified into 3 types: non-gated, directly gated and second messe nger gated channels. Among the important directly gated channels are voltag e gated (Na+, K+, Ca2+, Cl-) and ligand gated (ACh, Glutamate, GABA, Glycin e) channels. Channels are macromolecular protein complexes within the lipid membrane. They are divided into distinct protein units called subunits.. E ach subunit has a specific function and is encoded by a different gene. The following inherited channelopathies are described. (1) Sodium channelopath ies: familial generalized epilepsy with febrile seizures plus, hyperkalemic periodic paralysis, paramyotonias, hypokalemic periodic paralysis; (2) pot assium channelopathies: benign infantile epilepsy, episodic ataxia type I; (3) calcium channelopathies: episodic ataxia type 2, spinocerebellar ataxia type 6, familial hemiplegic migraine, hypokalemic periodic paralysis, cent ral core disease, malignant hyperthermia syndrome, congenital stationary ni ght blindness; (4) chloride channelopathies: myotonia congenitas: (5) ACh r eceptor channelopathies: autosomal dominant frontal lobe nocturnal epilepsy , congenital myasthenic syndromes; (6) glycine receptor channelopathies: hy perekplexia. Conclusions: Studies of human inherited channelopathies have clarified the functions of many ion channels. More than one gene may regulate a function in a channel, thus different genetic mutations may manifest with the same d isorder. The complex picture of the genetic and molecular structures of cha nnels will require frequent updates. (C) 2001 Elsevier Science ireland Ltd. All rights reserved.