Channelopathy
{{short description|Diseases caused by dysfunction of ion channels or related proteins}}
{{Infobox medical condition (new)
| name = Channelopathy
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| image = Ion channel image - Kim 2014 PMCID 3935107.png
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| caption = Sodium channel, implicated in channelopathies including Brugada syndrome, Long QT syndrome, Dravet syndrome, Paramyotonia congenita
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| field = Medical genetics, Neuromuscular medicine, Cardiology
| symptoms = Dependent on type. Include: Syncope, muscle weakness, seizures, breathlessness
| complications = Dependent on type. Include: Sudden death
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| causes = Genetic variants
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}}Channelopathies are a group of diseases caused by the dysfunction of ion channel subunits or their interacting proteins. These diseases can be inherited or acquired by other disorders, drugs, or toxins. Mutations in genes encoding ion channels, which impair channel function, are the most common cause of channelopathies. There are more than 400 genes that encode ion channels, found in all human cell types and are involved in almost all physiological processes.{{cite journal | vauthors = Imbrici P, Liantonio A, Camerino GM, De Bellis M, Camerino C, Mele A, Giustino A, Pierno S, De Luca A, Tricarico D, Desaphy JF, Conte D | display-authors = 6 | title = Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery | journal = Frontiers in Pharmacology | volume = 7 | pages = 121 | date = 2016-05-10 | pmid = 27242528 | pmc = 4861771 | doi = 10.3389/fphar.2016.00121 | doi-access = free }} Each type of channel is a multimeric complex of subunits encoded by a number of genes. Depending where the mutation occurs it may affect the gating, conductance, ion selectivity, or signal transduction of the channel.
Channelopathies can be categorized based on the organ system which they are associated with. In the cardiovascular system, the electrical impulse needed for each heartbeat is made possible by the electrochemical gradient of each heart cell. Because the heartbeat is dependent on the proper movement of ions across the surface membrane, cardiac channelopathies make up a key group of heart diseases.{{cite journal | vauthors = Marbán E | title = Cardiac channelopathies | journal = Nature | volume = 415 | issue = 6868 | pages = 213–218 | date = January 2002 | pmid = 11805845 | doi = 10.1038/415213a | s2cid = 4419017 | bibcode = 2002Natur.415..213M }} Long QT syndrome, the most common form of cardiac channelopathy, is characterized by prolonged ventricular repolarization, predisposing to a high risk of ventricular tachyarrhythmias (e.g., torsade de pointes), syncope, and sudden cardiac death.
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.
Causes
= Genetic type =
Mutations in genes encoding ion channels, which cause defects in channel function, are the most common cause of channelopathies.{{cite journal | vauthors = Kim JB | title = Channelopathies | journal = Korean Journal of Pediatrics | volume = 57 | issue = 1 | pages = 1–18 | date = January 2014 | pmid = 24578711 | pmc = 3935107 | doi = 10.3345/kjp.2014.57.1.1 }}
= Acquired type =
Types
The types in the following table are commonly accepted.{{By whom|date=November 2017}}{{citation needed|date=November 2017}} 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").{{Cite journal |last=Gadsby |first=David C. |date=May 2009 |title=Ion channels versus ion pumps: the principal difference, in principle |journal=Nature Reviews. Molecular Cell Biology |volume=10 |issue=5 |pages=344–352 |doi=10.1038/nrm2668 |issn=1471-0080 |pmc=2742554 |pmid=19339978}} 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.{{Cite journal |last1=Braz |first1=Luís |last2=Soares-Dos-Reis |first2=Ricardo |last3=Seabra |first3=Mafalda |last4=Silveira |first4=Fernando |last5=Guimarães |first5=Joana |date=October 2019 |title=Brody disease: when myotonia is not myotonia |url=https://pubmed.ncbi.nlm.nih.gov/30996034/ |journal=Practical Neurology |volume=19 |issue=5 |pages=417–419 |doi=10.1136/practneurol-2019-002224 |issn=1474-7766 |pmid=30996034|s2cid=122401141 }}
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{{Cite journal |last1=Smith |first1=Richard S. |last2=Kenny |first2=Connor J. |last3=Ganesh |first3=Vijay |last4=Jang |first4=Ahram |last5=Borges-Monroy |first5=Rebeca |last6=Partlow |first6=Jennifer N. |last7=Hill |first7=R. Sean |last8=Shin |first8=Taehwan |last9=Chen |first9=Allen Y. |last10=Doan |first10=Ryan N. |last11=Anttonen |first11=Anna-Kaisa |last12=Ignatius |first12=Jaakko |last13=Medne |first13=Livija |last14=Bönnemann |first14=Carsten G. |last15=Hecht |first15=Jonathan L. |date=2018-09-05 |title=Sodium channel SCN3A (NaV1.3) regulation of human cerebral cortical folding and oral motor development |journal=Neuron |volume=99 |issue=5 |pages=905–913.e7 |doi=10.1016/j.neuron.2018.07.052 |issn=0896-6273 |pmc=6226006 |pmid=30146301}} and the pump gene ATP1A3, among other genes that are not ion transporters.{{Cite journal |last1=Stutterd |first1=Chloe A. |last2=Leventer |first2=Richard J. |date=June 2014 |title=Polymicrogyria: a common and heterogeneous malformation of cortical development |url=https://pubmed.ncbi.nlm.nih.gov/24888723/ |journal=American Journal of Medical Genetics. Part C, Seminars in Medical Genetics |volume=166C |issue=2 |pages=227–239 |doi=10.1002/ajmg.c.31399 |issn=1552-4876 |pmid=24888723|s2cid=24534275 }}
See also
- Template: ATPase disorders (ion pumps)
References
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Bibliography
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- {{cite journal | vauthors = Song YW, Kim SJ, Heo TH, Kim MH, Kim JB | title = Normokalemic periodic paralysis is not a distinct disease | journal = Muscle & Nerve | volume = 46 | issue = 6 | pages = 914–916 | date = December 2012 | pmid = 22926674 | doi = 10.1002/mus.23441 | s2cid = 43821573 }}
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External links
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VIDEO [http://videos.med.wisc.edu/videoInfo.php?videoid=303 Channel Surfing in Pediatrics] by Carl E. Stafstrom, M.D., at the UW-Madison Health Sciences Learning Center.
- {{cite web | url = http://www.theweisslab.com | title = The Weiss Lab | access-date = | date = | work = The Weiss Lab is investigating the molecular and cellular mechanisms underlying human diseases caused by dysfunction of ion channels| pages = | quote = }}
- {{usurped|1=[https://web.archive.org/web/20110626161020/http://www.channelopathy-foundation.org/ The Channelopathy Foundation - Foundation for Ion Channel diseases]}}
- [http://www.cff.org Cystic Fibrosis Foundation]
- [https://web.archive.org/web/20090923023930/http://rarediseasesnetwork.epi.usf.edu/gdmcc/learnmore/index.htm#cf Rare Diseases Clinical Research Network]
{{Diseases of myoneural junction and muscle}}
{{Channelopathy}}{{Membrane transport}}