Channelopathy

Channelopathy
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 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.^[1] There are more than 400 genes that encode ion channels, found in all human cell types and are involved in almost all physiological processes.^[2] 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.^[3] 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.^[1]

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.

Mutations in genes encoding ion channels, which cause defects in channel function, are the most common cause of channelopathies.^[1]

Acquired channelopathies are caused by acquired disorders, drug use, toxins, etc.^[1]

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.

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").^[10] 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.^[10]

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.^[11]

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^[12] and the pump gene ATP1A3,^[6] among other genes that are not ion transporters.^[13]

• Template: ATPase disorders (ion pumps)

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