title: Ankyrin-B regulates Kir6.2 membrane expression and function in heart.
abstract: Ankyrin polypeptides are critical for normal membrane protein expression in diverse cell types, including neurons, myocytes, epithelia, and erythrocytes. Ankyrin dysfunction results in defects in membrane expression of ankyrin-binding partners (including ion channels, transporters, and cell adhesion molecules), resulting in aberrant cellular function and disease. Here, we identify a new role for ankyrin-B in cardiac cell biology. We demonstrate that cardiac sarcolemmal K(ATP) channels directly associate with ankyrin-B in heart via the K(ATP) channel alpha-subunit Kir6.2. We demonstrate that primary myocytes lacking ankyrin-B display defects in Kir6.2 protein expression, membrane expression, and function. Moreover, we demonstrate a secondary role for ankyrin-B in regulating K(ATP) channel gating. Finally, we demonstrate that ankyrin-B forms a membrane complex with K(ATP) channels and the cardiac Na/K-ATPase, a second key membrane transporter involved in the cardiac ischemia response. Collectively, our new findings define a new role for cardiac ankyrin polypeptides in regulation of ion channel membrane expression in heart.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors.forename: Jingdong
authors.initials: J
authors.lastname: Li
authors.forename: Crystal F
authors.initials: CF
authors.lastname: Kline
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hund
authors.forename: Mark E
authors.initials: ME
authors.lastname: Anderson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mohler
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis* / Q000097:blood*; D012508:Sarcolemma / Q000235:genetics / Q000378:metabolism; D000099161:Kcnj11 Channel
chemical_list: D017487:Ankyrins; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel; C498995:Ank2 protein, mouse