PT - JOURNAL ARTICLE AU - Char-Chang Shieh AU - Michael Coghlan AU - James P. Sullivan AU - Murali Gopalakrishnan TI - Potassium Channels: Molecular Defects, Diseases, and Therapeutic Opportunities DP - 2000 Dec 01 TA - Pharmacological Reviews PG - 557--594 VI - 52 IP - 4 4099 - http://pharmrev.aspetjournals.org/content/52/4/557.short 4100 - http://pharmrev.aspetjournals.org/content/52/4/557.full SO - Pharmacol Rev2000 Dec 01; 52 AB - Potassium channels play important roles in vital cellular signaling processes in both excitable and nonexcitable cells. Over 50 human genes encoding various K+ channels have been cloned during the past decade, and precise biophysical properties, subunit stoichiometry, channel assembly, and modulation by second messenger and ligands have been elucidated to a large extent. Recent advances in genetic linkage analysis have greatly facilitated the identification of many disease-producing loci, and naturally occurring mutations in various K+ channels have been identified in diseases such as long-QT syndromes, episodic ataxia/myokymia, familial convulsions, hearing and vestibular diseases, Bartter's syndrome, and familial persistent hyperinsulinemic hypoglycemia of infancy. In addition, changes in K+ channel function have been associated with cardiac hypertrophy and failure, apoptosis and oncogenesis, and various neurodegenerative and neuromuscular disorders. This review aims to 1) provide an understanding of K+ channel function at the molecular level in the context of disease processes and 2) discuss the progress, hurdles, challenges, and opportunities in the exploitation of K+ channels as therapeutic targets by pharmacological and emerging genetic approaches.