title: Potassium channel remodeling in cardiac hypertrophy.
abstract: Cardiac hypertrophy is an adaptive process against increased work loads; however, hypertrophy also presents substrates for lethal ventricular arrhythmias, resulting in sudden arrhythmic deaths that account for about one third of deaths in cardiac hypertrophy. To maintain physiological cardiac function in the face of increased work loads, hypertrophied cardiomyocytes undergo K(+) channel remodeling that provides a prolongation in action potential duration and an increase in Ca(2+) entry. Increased Ca(2+) entry, in turn, activates signaling mechanisms including a calcineruin/NFAT pathway to permit remodeling of the K(+) channels. This results in a positive feedback loop between the K(+) channel remodeling and altered Ca(2+) handling; this loop may represent a potential therapeutic target against sudden arrhythmic deaths in cardiac hypertrophy. The purposes of this review are to: (1) discuss types of K(+) channels and their mRNA that undergo remodeling in cardiac hypertrophy; (2) report on recent research on molecular mechanisms of K(+) channel remodeling; and (3) address physiological events underlying new therapeutic modalities to ameliorate arrhythmias and sudden death in cardiac hypertrophy.
authors.affiliation: Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan. t_furukawa.bip@mri.tmd.ac.jp
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Furukawa
authors.forename: Junko
authors.initials: J
authors.lastname: Kurokawa
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism*; D016757:Death, Sudden, Cardiac / Q000517:prevention & control*; D004195:Disease Models, Animal; D006801:Humans; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D015221:Potassium Channels; D012333:RNA, Messenger; D002118:Calcium