Home > A. Molecular pathology > channelopathies


Monday 29 September 2003

Definition: Channelopathies are diseases caused by inherited mutations of ion channels. Mutations of ion channels can thus theoretically alter the activation, ion selectivity, or inactivation of the corresponding mutated channel. Channelopathies can be classified according to the abnormal channel or affected organ (muscle or brain).

One characteristic of the channelopathies is a significant phenotypic overlap in clinical presentation, pathophysiology, and treatment. For example, patients with episodic ataxia type 2 have episodes of ataxia, but can alternatively have migraines and epilepsy.

The overlap observed in pathophysiology is mainly mediated through hyperexcitability of the neurons or muscle cells, leading to clinical symptoms such as seizures or myotonia.

Electrophysiologic investigations (electromyogram, electroencephalogram, and electrocardiogram) are useful in this group of diseases for demonstrating cellular hyperexcitability and correctly orient a specific diagnosis.

Most of these diseases have similar precipitants (stress, fatigue, and dietary factors), and are treated with medications selectively acting on specific ion channels (i.e., channel blockers).

Phenotypic heterogeneity

Different mutations in the same gene can cause different diseases (e.g., mutations in the same voltage-dependent sodium channel in skeletal muscle can result in hyperkalemic periodic paralysis, hypokalemic periodic paralysis, potassium-aggravated myotonia, and paramyotonia congenita).

Genetic heterogeneity

Mutations in different genes can result in the same apparent disease phenotype (e.g., hyperkalemic periodic paralysis is caused by mutations in different genes coding for the skeletal muscle sodium channel).

According to channel types

- K(+) channelopathies
- Na(+) channelopathies
- Ca(2+) channelopathies
- CRAC channelopathies

According to the localization

- cardial channelopathies
- endocrine channelopathies
- muscular channelopathies
- renal channelopathies


- Ion Channels and Disease: Channelopathies. by Frances M. Ashcroft. Hardcover: 481 pages ; Dimensions (in inches): 1.07 x 10.30 x 7.15. Publisher: Academic Press; 1st edition (January 15, 2000) ISBN: 0120653109


- Bernard G, Shevell MI. Channelopathies: a review. Pediatr Neurol. 2008 Feb;38(2):73-85. PMID: 18206787

- Foggia L, Hovnanian A. Calcium pump disorders of the skin. Am J Med Genet. 2004 Nov 15;131C(1):20-31. PMID: 15468148

- Hubner CA, Jentsch TJ. Ion channel diseases. Hum Mol Genet. 2002 Oct 1;11(20):2435-45. PMID: 12351579

- Bulman DE. Phenotype variation and newcomers in ion channel disorders. Hum Mol Genet. 1997;6(10):1679-85. PMID: 9300659

- Doyle JL, Stubbs L. Ataxia, arrhythmia and ion-channel gene defects. Trends Genet. 1998 Mar;14(3):92-8. PMID: 9540405