The channelopathies: an overview

Abstract

What at first glance appears to be a random selection of widely differing clinical presentations and syndromes, has recently been found to have as their common underlying factor an inherited abnormality of the mechanism in the cell wall, the ion channel, which is responsible for the transmembrane passage of various ions. Included in this diverse array of diseases are malignant hyperthermia, long QT syndrome, myotonia congenita, Eaton Lambert syndrome, certain forms of migraine and epilepsy, as well as cystic fibrosis.1The common pathophysiology in all these diseases is an inherited abnormality of the amino acid sequence of the complex protein structure from which the ion channel is composed. These ion channels are ubiquitous in the body, their expression is not restricted only to excitable cells such as neurons or myocytes, and they may be found in the external membrane as well as internal organelles of cells such as pancreatic and renal cells. Because each of these diseases is caused by a discrete abnormality of an ion channel protein, this diverse variety of clinical manifestations is grouped together and described as the channelopathies.2In order to better understand the pathophysiology involved in each of the channelopathies, it is necessary to review the normal physiology of the individual ion channels themselves.