Channelopathy

Causes

Genetic type

Mutations in genes encoding ion channels, which cause defects in channel function, are the most common cause of channelopathies.

Acquired type

Acquired channelopathies are caused by acquired disorders, drug use, toxins, etc.

Types

The types in the following table are commonly accepted. Channelopathies currently under research, like Kir4.1 potassium channel in multiple sclerosis, are not included.

Ion channels versus ion pumps

Both channels and pumps are ion transporters which move ions across membranes. Channels move ions quickly, through passive transport, down electrical and concentration gradients (moving "downhilll"); whereas pumps move ions slowly, through active transport, building-up gradients (moving "uphill"). Historically the difference between the two seemed cut and dried; however, recent research has shown that in some ion transporters, it is not always clear whether it functions as a channel or a pump.

Diseases involving ion pumps can produce symptoms similar to channelopathies, as they both involve the movement of ions across membranes. Brody disease (also known as Brody myopathy) includes symptoms similar to myotonia congenita, including muscle stiffness and cramping after initiating exercise (delayed muscle relaxation). However, it is pseudo-myotonia as those with Brody disease have normal EMG.

Due to similar symptoms, different genes for both channels and pumps can be associated with the same disease. For instance, polymicrogyria has been associated with the channel gene SCN3A and the pump gene ATP1A3, among other genes that are not ion transporters.

References

Bibliography

References

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2. (January 2002). "Cardiac channelopathies". Nature.
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4. (February 2012). "A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia". BMC Musculoskeletal Disorders.
5. (September 2018). "Sodium Channel SCN3A (Na_V1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development". Neuron.
6. (June 2021). "Early role for a Na⁺,K⁺-ATPase (''ATP1A3'') in brain development". Proceedings of the National Academy of Sciences of the United States of America.
7. (January 2015). "Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy". Nature Genetics.
8. (January 2009). "Seizures and arrhythmias: Differing phenotypes of a common channelopathy?". Neurology.
9. (April 2003). "Channelopathies as a genetic cause of epilepsy". Current Opinion in Neurology.
10. Gadsby, David C.. (May 2009). "Ion channels versus ion pumps: the principal difference, in principle". Nature Reviews. Molecular Cell Biology.
11. (October 2019). "Brody disease: when myotonia is not myotonia". Practical Neurology.
12. (2018-09-05). "Sodium channel SCN3A (NaV1.3) regulation of human cerebral cortical folding and oral motor development". Neuron.
13. (June 2014). "Polymicrogyria: a common and heterogeneous malformation of cortical development". American Journal of Medical Genetics. Part C, Seminars in Medical Genetics.