Potassium channels: molecular defects, diseases, and therapeutic opportunities.
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.
Shieh
C C
CC
Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA. char-chang.shieh@abbott.com
Coghlan
M
M
Sullivan
J P
JP
Gopalakrishnan
M
M
D000544:Alzheimer Disease / Q000209:etiology; D000818:Animals; D017209:Apoptosis; D006311:Hearing Disorders / Q000209:etiology; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology; D008133:Long QT Syndrome / Q000209:etiology; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D015221:Potassium Channels