What is a channelopathy?

Channelopathies are diseases that are grouped together due to the problems that cause them. When an ion channel goes wrong or does not function as it should, it may produce a disease in an individual. Certain forms of skeletal and cardiac muscle and brain diseases such as the myotonias, epilepsies, migraine or arrhythmias are due to pathological alterations in channel proteins and thus, can be considered as "Channelopathies".

The revelation that such a diversity of diseases are associated with channel dysfunction has been made possible by recent advances in medicine. These studies have also dramatically increased our understanding of how ion channels function under normal circumstances. Given that the diversity of ion channels is large, it seems likely that more diseases will become recognised as channelopathies in the future requiring and leading to the more detailed characterisation of additional ion channels.

These diseases are usually caused by mutations in ion channel encoding genes that disrupt channel function. Many of these mutations produce changes in channel gating, i.e. they make the channels open more or less frequently which affects the excitability of the affected tissue.

Another important cause of channelopathies is auto-immune attack. However, mutations in associated proteins, alterations in the expression of ion channels, and changes in the activity of non-mutated channel genes or associated proteins can also produce what are known as acquired channelopathies. Such acquired channelopathies may occur as a result of nerve-injury or after drug treatments that perturb cellular function.

This huge variety in the causes of channelopathies, as varied as the diseases themselves, not only makes it difficult to study these diseases but it often makes the clinical diagnosis of these diseases problematic.

Most channelopathies are typically provoked by triggers and only few lead to permanent disability. Typically the symptoms occur as episodic attacks lasting from minutes to days that show spontaneous and complete remission.

Well known examples of channelopathies are: diseases of skeletal muscle such as the myotonias - periodic paralyses and malignant hyperthermia; central nervous disorders of excitability - the episodic ataxias, familiar hemiplegic migraines, as well as three forms of dominantly inherited epilepsies; cardiac arrhythmias - the long-QT syndromes and idiopathic ventricular fibrillation; and cystic fibrosis.

Included amongst the Channelopathies are intermittent diseases in people who are otherwise healthy and active (eg, epilepsy, migraine, arrhytmia), more debilitating illnesses (such as muscular disorders, deafness, blindness, Rasmussen's encephalitis), and even some rare disorders like periodic paralysis. List of channelopathies

As stated, Channelopathies may also be due to the body producing antibodies that destroy specific ion channel proteins. These types of disease are known as autoimmune channelopathies of which myasthenia gravis and neuromyotonia are good examples. In these diseases, the antibodies mainly affect the function of the nicotinic acetylcholine receptors at the endplate and dendrotoxin-sensitive potassium channels, respectively.

A greater insight into the structure and function of ion channels will be crucial to understanding the pathophysiology of these conditions. Significant advances have been made in determining the structure of some channels at atomic resolution. When coupled to the power of the biophysical techniques to study these kind of proteins, the potential to increase our understanding of the complex biological processes and pathologies is greatly magnified, as is our capacity to develop new therapeutic agents.

In conclusion, the more we study these poorly understood diseases, the closer we will come to discovering suitable therapies.