Channelopathy
Channelopathy | |
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Sodium channel, implicated in channelopathies including Brugada syndrome, Long QT syndrome, Dravet syndrome, Paramyotonia congenita | |
Specialty | Medical genetics, Neuromuscular medicine, Cardiology |
Symptoms | Dependent on type. Include: Syncope, muscle weakness, seizures, breathlessness |
Complications | Dependent on type. Include: Sudden death |
Causes | Genetic variants |
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 many 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.
Types[]
The types in the following table are commonly accepted.[by whom?][citation needed] Channelopathies currently under research, like Kir4.1 potassium channel in multiple sclerosis, are not included.
![Prenatal Channelopathy](http://upload.wikimedia.org/wikipedia/commons/thumb/a/ad/Channelopathies.png/640px-Channelopathies.png)
Condition | Channel type |
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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 |
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] ATP1A3[6] |
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[7][8] |
References[]
- ^ Kim JB (January 2014). "Channelopathies". Korean Journal of Pediatrics. 57 (1): 1–18. doi:10.3345/kjp.2014.57.1.1. PMC 3935107. PMID 24578711.
- ^ Kass RS (August 2005). "The channelopathies: novel insights into molecular and genetic mechanisms of human disease". The 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, Vargas A, Martinez A, Vallejo M, Martinez-Lavin M (February 2012). "A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia". BMC Musculoskeletal Disorders. 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 MC, Mancini GM, Sztriha L, Im K, Amrom D, Andermann E, Paetau R, Lehesjoki AE, Walsh CA, Lehtinen MK (September 2018). "V1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development". Neuron. 99 (5): 905–913.e7. doi:10.1016/j.neuron.2018.07.052. PMC 6226006. PMID 30146301.
- ^ Smith RS, Florio M, Akula SK, Neil JE, Wang Y, Hill RS, et al. (2021-06-22). "Early role for a Na + ,K + -ATPase ( ATP1A3 ) in brain development". Proceedings of the National Academy of Sciences. 118 (25): e2023333118. doi:10.1073/pnas.2023333118. PMC 8237684. PMID 34161264.
- ^ 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. S2CID 207103822.
- ^ 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. S2CID 40441842.
Bibliography[]
- Song YW, Kim SJ, Heo TH, Kim MH, Kim JB (December 2012). "Normokalemic periodic paralysis is not a distinct disease". Muscle & Nerve. 46 (6): 914–6. doi:10.1002/mus.23441. PMID 22926674. S2CID 43821573.
External links[]
Classification |
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VIDEO Channel Surfing in Pediatrics by Carl E. Stafstrom, M.D., at the UW-Madison Health Sciences Learning Center.
- "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
- Cystic Fibrosis Foundation
- Rare Diseases Clinical Research Network
- Channelopathies