Channelopathies are diseases caused by disturbed function of ion channel

Ion channel

Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...

 subunits or the proteins that regulate them. These diseases may be either congenital (often resulting from a mutation

Mutation

In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

 or mutations in the encoding genes) or acquired (often resulting from autoimmune attack on an ion channel

Ion channel

Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...

).

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

Hyperkalemic periodic paralysis

Hyperkalemic periodic paralysis is a genetic disorder which occurs in both humans and horses, where it is also known as Impressive Syndrome. It is an inherited autosomal dominant disorder which affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood...

, was first identified in the descendants of Impressive

Impressive (horse)

Impressive was born an Appendix American Quarter Horse, however earned his full AQHA registration in 1971. He was the 1974 World Champion Open Aged halter stallion, the first such World Champion in his breed, despite carrying only 48 halter points in total. He is famous for his highly successful...

, a registered Quarter Horse (see AQHA website).

The channelopathies of human skeletal muscle

Skeletal muscle

Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...

 include hyper-, hypo- and normokalemic (high, low and normal potassium blood concentrations) periodic paralysis

Periodic paralysis

Periodic paralysis is a group of rare genetic diseases that lead to weakness or paralysis from common triggers such as cold, heat, high carbohydrate meals, not eating, stress or excitement and physical activity of any kind...

, myotonia congenita

Myotonia congenita

Congenital myotonia is a genetic, neuromuscular channelopathy that affects skeletal muscles . It is congenital, meaning that it is present from birth. Amongst other problems, it causes delayed relaxation of the muscles and rigidity...

 and paramyotonia congenita

Paramyotonia congenita

Paramyotonia Congenita , also known as Paramyotonia congenita of von Eulenburg or Eulenburg disease, is a rare congenital autosomal dominant neuromuscular disorder characterized by “paradoxical” myotonia...

.

Types

Condition	Channel type
Alternating hemiplegia of childhood Alternating hemiplegia of childhood Alternating hemiplegia of childhood is a rare neurological disorder of uncertain etiology, which is named for the transient episodes, often referred to as attacks, of hemiplegia from which those with the disorder suffer. These hemiplegic attacks can cause anything from mild weakness to complete...	Na⁺/K⁺-ATPase
Bartter syndrome Bartter syndrome Bartter syndrome is a rare inherited defect in the thick ascending limb of the loop of Henle. It is characterized by low potassium levels , increased blood pH , and normal to low blood pressure. There are two types of Bartter syndrome: neonatal and classic...	various by type
Brugada syndrome Brugada syndrome The Brugada syndrome is a genetic disease that is characterised by abnormal electrocardiogram findings and an increased risk of sudden cardiac death. It is named by the Spanish cardiologists Pedro Brugada and Josep Brugada...	various, by type
Congenital hyperinsulinism Congenital hyperinsulinism Congenital hyperinsulinism is a medical term referring to a variety of congenital disorders in which hypoglycemia is caused by excessive insulin secretion. Congenital forms of hyperinsulinemic hypoglycemia can be transient or persistent, mild or severe. These conditions are present at birth and...	Inward-rectifier potassium ion channel Inward-rectifier potassium ion channel Inwardly rectifying potassium channels are a specific subset of potassium selective ion channels. To date, seven subfamilies have been identified in various mammalian cell types...
Cystic fibrosis Cystic fibrosis Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...	Chloride channel
Dravet Syndrome Generalized epilepsy with febrile seizures plus Generalized epilepsy with febrile seizures plus is a syndromic autosomal dominant disorder where afflicted individuals can exhibit numerous epilepsy phenotypes. GEFS+ can persist beyond early childhood...	Voltage-gated sodium channel
Episodic Ataxia Episodic ataxia Episodic ataxia is an autosomal dominant disorder characterized by sporadic bouts of ataxia with or without myokymia . There are seven types recognised but the majority are due to two recognized entities. Ataxia can be provoked by stress, startle, or heavy exertion such as exercise. Symptoms can...	Voltage-gated potassium channel Voltage-gated potassium channel Voltage-gated potassium channels are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state....
Erythromelalgia Erythromelalgia Erythromelalgia, also known as Mitchell's disease , acromelalgia, red neuralgia, or erythermalgia, is a rare neurovascular peripheral pain disorder in which blood vessels, usually in the lower extremities , are episodically blocked , then become hyperemic and inflamed...	Voltage-gated sodium channel
Generalized epilepsy with febrile seizures plus Generalized epilepsy with febrile seizures plus Generalized epilepsy with febrile seizures plus is a syndromic autosomal dominant disorder where afflicted individuals can exhibit numerous epilepsy phenotypes. GEFS+ can persist beyond early childhood...	Voltage-gated sodium channel
Familial hemiplegic migraine Familial hemiplegic migraine Familial hemiplegic migraine is an autosomal dominant classical migraine subtype that typically includes hemiparesis during the aura phase. It can be accompanied by other symptoms, such as ataxia, coma and epileptic seizures...	various
Hyperkalemic periodic paralysis Hyperkalemic periodic paralysis Hyperkalemic periodic paralysis is a genetic disorder which occurs in both humans and horses, where it is also known as Impressive Syndrome. It is an inherited autosomal dominant disorder which affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood...	Voltage-gated sodium channel
Hypokalemic periodic paralysis Hypokalemic periodic paralysis Hypokalemic periodic paralysis is a rare channelopathy characterized by muscle weakness or paralysis with a matching fall in potassium levels in the blood...	Voltage-gated sodium channel or voltage-dependent calcium channel Voltage-dependent calcium channel Voltage-dependent calcium channels are a group of voltage-gated ion channels found in excitable cells with a permeability to the ion Ca2+...  (calciumopathy Calciumopathy A calciumopathy is a disease caused by disruption to the use of calcium within a cell. To a large extent, a calciumopathy is a type of channelopathy, or a disease caused by disturbed function of ion channel subunits or the proteins that regulate them; calciumopathies also include dysfunctions of... )
Long QT syndrome Long QT syndrome The long QT syndrome is a rare inborn heart condition in which delayed repolarization of the heart following a heartbeat increases the risk of episodes of torsade de pointes . These episodes may lead to palpitations, fainting and sudden death due to ventricular fibrillation... main type Romano-Ward syndrome Romano-Ward syndrome Romano-Ward syndrome, is the major variant of long QT syndrome. It is a condition that causes a disruption of the heart's normal rhythm. This disorder is a form of long QT syndrome, which is a heart condition that causes the cardiac muscle to take longer than usual to recharge between beats...	various, by type
Malignant hyperthermia Malignant hyperthermia Malignant hyperthermia or malignant hyperpyrexia is a rare life-threatening condition that is usually triggered by exposure to certain drugs used for general anesthesia; specifically, the volatile anesthetic agents and the neuromuscular blocking agent, succinylcholine...	Ligand-gated calcium channel
Mucolipidosis type IV Mucolipidosis type IV Mucolipidosis type IV is an autosomal recessive lysosomal storage disorder. Individuals with the disorder have many symptoms including delayed psychomotor development and various ocular aberrations. The disorder is caused by mutations in the MCOLN1 gene, which encodes a non-selective cation...	Non-selective cation channel
Myasthenia Gravis Myasthenia gravis Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...	Ligand-gated sodium channel
Myotonia congenita Myotonia congenita Congenital myotonia is a genetic, neuromuscular channelopathy that affects skeletal muscles . It is congenital, meaning that it is present from birth. Amongst other problems, it causes delayed relaxation of the muscles and rigidity...	Voltage-dependent chloride channel
Neuromyotonia Neuromyotonia Neuromyotonia , also known as Isaacs' syndrome, is a form of peripheral nerve hyperexcitability that causes spontaneous muscular activity resulting from repetitive motor unit action potentials of peripheral origin.-Causes:...	Voltage-gated potassium channel
Nonsyndromic deafness Nonsyndromic deafness Nonsyndromic deafness is hearing loss that is not associated with other signs and symptoms. In contrast, syndromic deafness involves hearing loss that occurs with abnormalities in other parts of the body....	various
Paramyotonia congenita Paramyotonia congenita Paramyotonia Congenita , also known as Paramyotonia congenita of von Eulenburg or Eulenburg disease, is a rare congenital autosomal dominant neuromuscular disorder characterized by “paradoxical” myotonia...	Voltage-gated sodium channel
Retinitis pigmentosa Retinitis pigmentosa Retinitis pigmentosa is a group of genetic eye conditions that leads to incurable blindness. In the progression of symptoms for RP, night blindness generally precedes tunnel vision by years or even decades. Many people with RP do not become legally blind until their 40s or 50s and retain some...	Ligand-gated non-specific ion channels
Short QT syndrome Short QT syndrome Short QT syndrome is a genetic disease of the electrical system of the heart. It consists of a constellation of signs and symptoms, consisting of a short QT interval on an EKG that does not significantly change with heart rate, tall and peaked T waves, and a structurally normal heart...	various potassium channels suspected
Timothy syndrome Timothy syndrome Timothy syndrome is a rare autosomal dominant disorder characterized by physical malformations, as well as neurological and developmental defects, including heart QT-prolongation, heart arrhythmias, structural heart defects, syndactyly and autism spectrum disorders.Timothy syndrome often ends in...	Voltage-dependent calcium channel
Seizure Seizure An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...	Voltage-dependent potassium channel

External links

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

• The Channelopathy Foundation - Foundation for Ion Channel diseases
• Cystic Fibrosis Foundation
• Rare Diseases Clinical Research Network