The first ion channel was cloned in 1982 (Nature, 299, 793–797 and EMBO J., 1, 713–717). Since then, advances in molecular biology and genetics have led to the discovery of many other ion channel genes. Diseases associated with the malfunction of ion channels, or proteins that regulate them, belong to a protein 'class' that are important for the flux of ions into and out of virtually every living cell. Channelopathies are a group of disorders resulting from the dysfunction of ion channels located in the membranes of all cells and cellular organelles. Data derived from the Human Genome Project suggest that several hundreds of different ion channel genes exist and that each of them encodes a specific ion channel subunit which assembles with other subunits forming functionally active membrane pores selective for specific ions. The ion channel associated diseases can be either congenital or acquired. Inherited channelopathies often result from mutations in the encoding gene sequences. Autoimmune dysfunction or administration of drugs can be the reasons for acquired forms of channelopathies.

Although many people associate ion channels only with excitable tissues, their function is not at all restricted to neurons or muscle. The important, and at first surprising, functions of ion channels in other tissues are now evident from human channelopathies and mouse knockout models.

An incomplete list of diseases derived by dysfunctional ion channels include:

 

In the nervous system

- generalized epilepsy with febrile seizures

- familial hemiplegic migraine

- episodic ataxia

- hyperkalemic and hypokalemic periodic paralysis

In the cardiovascular system:

- long QT syndrome

- short QT syndrome

- Brugada syndrome

- catecholaminergic polymorphic ventricular tachycardia

In the respiratory system:

- cystic fibrosis

In the endocrine system:

- neonatal diabetes mellitus

- familial hyperinsulinemic hypoglycemia

- thyrotoxic hypokalemic periodic paralysis

- familial hyperaldosteronism

In the urinary system:

- Bartter syndrome

- nephrogenic diabetes insipidus

-  autosomal-dominant polycystic kidney disease

- hypomagnesemia with secondary hypocalcemia

- Liddles syndrome

In the immune system:

- myasthenia gravis

- neuromyelitis optica

- Isaac syndrome

- anti-NMDA [N-methyl-D-aspartate] receptor encephalitis

The field of channelopathies is expanding rapidly, as is the utility of molecular-genetic and electrophysiological studies.