Channelopathies are diseases caused by disturbed function of ion channel subunits or the proteins that regulate them.[1][2]These diseases may be either congenital (often resulting from a mutation or mutations in the encoding genes) or acquired[3](often resulting from autoimmune attack on an ion channel).
There are a large number of distinct dysfunctions known to be caused by ion channel mutations. The genes for the construction of ion channels are highly conserved amongst mammals and one condition, hyperkalemic periodic paralysis, was first identified in the descendants of Impressive, a registered Quarter Horse.
The channelopathies of human skeletal muscle include hyper- and hypokalemic (high and low potassium blood concentrations) periodic paralysis, myotonia congenita and paramyotonia congenita.
Channelopathies affecting synaptic function are a type of synaptopathy.
The types in the following table are commonly accepted. Channelopathies currently under research, like Kir4.1 potassium channel in multiple sclerosis, are not included.
| Condition | Channel type |
|---|---|
| Alternating hemiplegia of childhood | Na⁺/K⁺-ATPase |
| Bartter syndrome | various by type |
| Brugada syndrome | various, by type |
| Catecholaminergic polymorphic ventricular tachycardia (CPVT) | Ryanodine receptor |
| Congenital hyperinsulinism | Inward-rectifier potassium ion channel |
| Cystic fibrosis | Chloride channel |
| Dravet Syndrome | Voltage-gated sodium channel |
| Episodic Ataxia | Voltage-gated potassium channel |
| Erythromelalgia | Voltage-gated sodium channel |
| Generalized epilepsy with febrile seizures plus | Voltage-gated sodium channel |
| Familial hemiplegic migraine | various |
| Associated with one particular disabling form of Fibromyalgia[4] | Voltage-gated sodium channel |
| Hyperkalemic periodic paralysis | Voltage-gated sodium channel |
| Hypokalemic periodic paralysis | Voltage-gated sodium channel or voltage-dependent calcium channel (calciumopathy) |
| Lambert-Eaton myasthenic syndrome | Voltage-gated calcium channel |
| Long QT syndrome main type Romano-Ward syndrome |
various, by type |
| Malignant hyperthermia | Ligand-gated calcium channel |
| Mucolipidosis type IV | Non-selective cation channel |
| Myotonia congenita | Voltage-dependent chloride channel |
| Neuromyelitis optica | Aquaporin-4 water channel |
| Neuromyotonia | Voltage-gated potassium channel |
| Nonsyndromic deafness | various |
Paramyotonia congenita
|
Voltage-gated sodium channel |
| Polymicrogyria (Brain Malformation) | Voltage-gated sodium channel, SCN3A [5] |
Retinitis pigmentosa
|
Ligand-gated non-specific ion channels |
| Short QT syndrome | various potassium channels suspected |
| Timothy syndrome | Voltage-dependent calcium channel |
| Tinnitus | Voltage-gated potassium channel of the KCNQ family |
| Seizure | Voltage-dependent potassium channel[6][7] |
Text under construction
References
- ^ Kim, JB (2014). “channelopathies”. Korean Journal of Pediatrics. 57 (1): 1–18. doi:10.3345/kjp.2014.57.1.1. PMC 3935107. PMID 24578711.
- ^ Robert S. Kass (2005). “The channelopathies: novel insights into molecular and genetic mechanisms of human disease”. Journal of Clinical Investigation. 115 (8): 1986–9. doi:10.1172/JCI26011. PMC 1180558. PMID 16075038.
- ^ Sid Gilman (2007). Neurobiology of Disease. Academic Press. pp. 319–. ISBN 978-0-12-088592-3. Retrieved 22 November 2010.
- ^ Vargas-Alarcon G, Alvarez-Leon E, Fragoso JM, et al. (2012). “A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia”. J Rheumatol Suppl. 19: 13:23. doi:10.1186/1471-2474-13-23. PMC 3310736. PMID 22348792.
- ^ Smith, RS; Kenny, CJ; Ganesh, V; Jang, A; Borges-Monroy, R; Partlow, JN; Hill, RS; Shin, T; Chen, AY; Doan, RN; Anttonen, AK; Ignatius, J; Medne, L; Bönnemann, CG; Hecht, JL; Salonen, O; Barkovich, AJ; Poduri, A; Wilke, M; de Wit, MCY; Mancini, GMS; Sztriha, L; Im, K; Amrom, D; Andermann, E; Paetau, R; Lehesjoki, AE; Walsh, CA; Lehtinen, MK (5 September 2018). “Sodium Channel SCN3A (NaV1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development”. Neuron. 99 (5): 905–913.e7. doi:10.1016/j.neuron.2018.07.052. PMID 30146301.
- ^ Hunter JV, Moss AJ (January 2009). “Seizures and arrhythmias: Differing phenotypes of a common channelopathy?”. Neurology. 72 (3): 208–9. doi:10.1212/01.wnl.0000339490.98283.c5. PMID 19153369. Retrieved 2009-04-30.
- ^ Mulley JC, Scheffer IE, Petrou S, Berkovic SF (April 2003). “Channelopathies as a genetic cause of epilepsy”. Current Opinion in Neurology. 16 (2): 171–6. doi:10.1097/00019052-200304000-00009. PMID 12644745. Retrieved 2009-04-30.
- Song, YW; Kim, SJ; Heo, TH; Kim, MH; Kim, JB (2012). “Normokalemic periodic paralysis is not a distinct disease”. Muscle & Nerve. 46 (6): 908–913. doi:10.1002/mus.23441. PMID 22926674.
VIDEO Channel Surfing in Pediatrics by Carl E. Stafstrom, M.D., at the UW-Madison Health Sciences Learning Center. http://videos.med.wisc.edu/videos/303
“The Weiss Lab”. The Weiss Lab is investigating the molecular and cellular mechanisms underlying human diseases caused by dysfunction of ion channels.
The Channelopathy Foundation – Foundation for Ion Channel diseases
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