12 - Ion channel disorders

Abstract

The ion channel disorders include epilepsy, ataxia, and neuromuscular disorders. These disorders result from mutations in the genes encoding either voltage-gated or ligand-gated ion channels and are also known as channelopathies. Mutations in six different types of channels or receptors have been identified as causing epilepsy. These include voltage-gated sodium, potassium, calcium, and chloride channels and receptors for acetylcholine (Ach) and γ-aminobutyric acid (GABA). The channelopathies that have been identified for causing ataxia include disorders of potassium and calcium channels, resulting in episodic ataxia types 1 (EA-1) and 2 (EA-2), and spinocerebellar ataxia 6 (SCA6). The ataxia syndromes are caused by mutations in genes encoding the primary pore-forming subunits of two ion channel genes; KCNA1 gene encoding the subunit of the KV1.1 potassium channel cause EA-1, and mutations in the CACNA1A gene encoding the α subunit of the CaV2.1 calcium channel cause EA-2 and SCA6. Ion channel mutations that alter the electrical excitability of skeletal muscle result in two related disorders: periodic paralyses and nondystrophic myotonias. The periodic paralyses are caused by mutations in three different ion channel genes. Mutations in the SCN4A gene encoding the Nav1.4 sodium channel cause hyperkalemic periodic paralysis (HyperPP) and hypokalemic periodic paralysis (HypoPP). The nondystrophic myotonias are caused by mutations in two genes. Mutations in the SCN4A sodium channel gene cause both paramyotonia congenita (PMC) and potassium aggravated myotonia (PAM).