Channelopathies are a group of diseases caused by the dysfunction of

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...

subunits or their interacting

proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

. These diseases can be inherited or acquired by other disorders, drugs, or toxins. Mutations in

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s encoding

s, 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. Each type of channel is a multimeric complex of subunits encoded by a number of genes. Depending where the

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

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 An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and th ...

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.

Long QT syndrome Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainting, d ...

, 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 Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

include hyper- and hypokalemic (high and low potassium blood concentrations)

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. The underlying mechanis ...

myotonia congenita Myotonia congenita is a congenital neuromuscular channelopathy that affects skeletal muscles (muscles used for movement). It is a genetic disorder. The hallmark of the disease is the failure of initiated contraction to terminate, often referred to ...

and

paramyotonia congenita Paramyotonia congenita (PC) is a rare congenital autosomal dominant neuromuscular disorder characterized by "paradoxical" myotonia. This type of myotonia has been termed paradoxical because it becomes worse with exercise whereas classical myotonia, ...

. Channelopathies affecting synaptic function are a type of

synaptopathy A synaptopathy is a disease of the brain, spinal cord or peripheral nervous system relating to the dysfunction of synapses. This can arise as a result of a mutation in a gene encoding a synaptic protein such as an ion channel, neurotransmitter ...

Causes

Genetic type

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

Acquired type

Acquired channelopathies are caused by acquired disorders, drug use, toxins, etc.

Types

The types in the following table are commonly accepted. Channelopathies currently under research, like Kir4.1 potassium channel in

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

, are not included.

References

Bibliography

External links

VIDE
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

{{Channelopathy *