title: Regulation of the ankyrin-B-based targeting pathway following myocardial infarction.
abstract: OBJECTIVE
  Ion channel reorganization is a critical step in the pro-arrhythmogenic remodelling process that occurs in heart disease. Ankyrin-B (AnkB) is required for targeting and stabilizing ion channels, exchangers, and pumps. Despite a wealth of knowledge implicating the importance of AnkB in human cardiovascular physiology, nothing is known regarding the role of AnkB in common forms of acquired human disease.
  
  
  RESULTS
  We present the first report of AnkB regulation following myocardial infarction (MI). AnkB protein levels were reduced in the infarct border zone 5 days following coronary artery occlusion in the canine. We also observed a dramatic increase in AnkB mRNA levels 5 days post-occlusion. Surprisingly, the expression of the upstream AnkB cytoskeletal component beta2-spectrin was unchanged in post-infarct tissues. However, protein levels and/or membrane expression of downstream AnkB-associated ion channels and transporters Na+/K+ ATPase, Na+/Ca2+ exchanger, and IP3 receptor were altered 5 days post-occlusion. Interestingly, protein levels of the protein phosphatase 2A, an AnkB-associated signalling protein, were significantly affected 5 days post-occlusion. AnkB and PP2A protein levels recovered by 14 days post-occlusion, whereas Na+/K+ ATPase levels recovered by 2 months post-occlusion.
  
  
  CONCLUSIONS
  These findings reveal the first evidence of ankyrin remodelling following MI and suggest an unexpected divergence point for regulation between ankyrin and the underlying cytoskeletal network. These findings suggest a logical, but unexpected, molecular mechanism underlying ion channel and transporter remodelling following MI.
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Iowa Carver College of Medicine, 285 Newton Road, CBRB 2283, Iowa City, IA 52242, USA. thomas-hund@uiowa.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hund
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Wright
authors.forename: Wen
authors.initials: W
authors.lastname: Dun
authors.forename: Jedidiah S
authors.initials: JS
authors.lastname: Snyder
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Boyden
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mohler
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D054648:Protein Phosphatase 2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors
chemical_list: D017487:Ankyrins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D012333:RNA, Messenger; D019831:Sodium-Calcium Exchanger; D054648:Protein Phosphatase 2; D000254:Sodium-Potassium-Exchanging ATPase