Genetics, an alternative way to discover, characterize and understand ion channels

1. The conventional approach to understanding the structure and propel ties of ion channels has been to use physiological characterization. 2, Purification and molecular cloning of ion channel genes has enabled more detailed structure-function analyses to be undertaken, 3, An alternative approach to the identification of genes of pathophysiolog ical importance has been the use of genetic linkage approaches and position al cloning or positional candidate analysis of ion channel genes. 4. Using genetic approaches, mutations have been described that cause inher ited neurological disorders of neurons (e.g. epilepsy, migraine, deafness, ataxia and startle disease), skeletal muscle (myotonia, malignant hyperther mia, periodic paralysis and myasthenia) and cardiac muscle (long QT syndrom e and ventricular fibrillation), 5. For each disease, gene structure-function analyses of the mutant alleles have provided further insights into the biology of ion channels. 6. The pr esent brief review examines the methods used in genetic linkage studies and positional cloning of disease genes. Understanding hom ion channel gene mu tations give rise to dysfunctional channels will be important in defining a nd treating the episodic and chronic channelopathies.