RT Journal Article
SR Electronic
T1 Potassium Channels: Molecular Defects, Diseases, and Therapeutic Opportunities
JF Pharmacological Reviews
JO Pharmacol Rev
FD American Society for Pharmacology and Experimental Therapeutics
SP 557
OP 594
VO 52
IS 4
A1 Char-Chang Shieh
A1 Michael Coghlan
A1 James P. Sullivan
A1 Murali Gopalakrishnan
YR 2000
UL http://pharmrev.aspetjournals.org/content/52/4/557.abstract
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.