Ligand-gated ion channelopathies: mutations in different genes causing one disease.

Abstract

It has been less than a decade since the first ion channel mutations causing a human hyperexcitability phenotype were identified.1,2⇓ These disorders have now come to be known as the channelopathies, a family of disorders that has grown tremendously over the last 9 years. Many of the channelopathies that have been characterized are caused by mutations in voltage-gated ion channels. The phenotypes that can result range from periodic paralysis, myotonia, episodic movement disorders, and cardiac dysrhythmias to epilepsy and migraine.3 Characterization of such ion channel mutations has led to a better understanding of the pathophysiology of these episodic diseases of the skeletal muscle, heart, and brain. In addition, the study of naturally occurring mutations in ion channels has led to new insights into the structure and function of this fascinating superfamily of proteins. However, voltage-gated ion channels are not the only primary determinants of membrane excitability. Ligand-gated ion channels …