Channelopathy

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).

Channelopathy
Sodium channel, implicated in channelopathies including Brugada syndrome, Long QT syndrome, Dravet syndrome, Paramyotonia congenita
SpecialtyMedical genetics, Neuromuscular medicine, Cardiology
SymptomsDependent on type. Include: Syncope, muscle weakness, seizures, breathlessness
ComplicationsDependent on type. Include: Sudden death
CausesGenetic variants

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. 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
(a periodic paralysis)
 Voltage-gated sodium channel
Polymicrogyria (Brain Malformation) Voltage-gated sodium channel, SCN3A [5]
Retinitis pigmentosa
(some forms)
 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]

References
  1. 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.
  2. 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.
  3. Sid Gilman (2007). Neurobiology of Disease. Academic Press. pp. 319–. ISBN 978-0-12-088592-3. Retrieved 22 November 2010.
  4. 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.
  5. 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.
  6. 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.
  7. 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.

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.
Classification

VIDEO Channel Surfing in Pediatrics by Carl E. Stafstrom, M.D., at the UW-Madison Health Sciences Learning Center.

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