Potassium channels: Molecular defects, diseases, and therapeutic opportunities

Potassium channels play important roles in vital cellular signaling process es in both excitable and nonexcitable cells. Over 50 human genes encoding v arious K+ channels have been cloned during the past decade, and precise bio physical properties, subunit stoichiometry, channel assembly, and modulatio n by second messenger and ligands have been elucidated to a large extent. R ecent advances in genetic linkage analysis have greatly facilitated the ide ntification of many disease-producing loci, and naturally occurring mutatio ns in various K+ channels have been identified in diseases such as long-QT syndromes, episodic ataxia/myokymia, familial convulsions, hearing and vest ibular diseases, Bartter's syndrome, and familial persistent hyperinsulinem ic hypoglycemia of infancy. In addition, changes in K+ channel function hav e been associated with cardiac hypertrophy and failure, apoptosis and oncog enesis, and various neurodegenerative and neuromuscular disorders. This rev iew aims to 1) provide an understanding of K+ channel function at the molec ular 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.