title: From global to local:  a new understanding of cardiac electromechanical coupling.
abstract: BACKGROUND
  The coupling between depolarisation and the heart's contraction is fundamental to the physiology and pathophysiology of the heart. This paper describes how the coupling depends on the interaction between proteins in "microdomains" in the heart muscle cells.
  
  
  METHODS
  The paper is based on the authors'' own research and on a discretionary selection of articles found by means of a literature search in PubMed.
  
  
  RESULTS
  Essential aspects of the physiology and pathophysiology of the heart must be understood through the interaction between proteins in delimited parts of the cells. The significance of the binding protein ankyrin-B and the Ca2+ channel IP3R (inositol 1,4,5-triphosphate receptor) is best understood in this context. Abnormal function of ankyrin-B and IP3R is involved in congenital diseases with increased risk of arrhythmia and in weakened contractility and arrhythmia in connection with heart failure. The pathophysiological mechanism involves a change in Ca2+ homeostasis locally in the heart muscle cells.
  
  
  CONCLUSIONS
  Normal cardiac electromechanical coupling depends on control of ionic homeostasis in intracellular microdomains. Insight into the interaction between proteins in these "local neighbourhoods" provides new explanations for the pathophysiology of heart disease and paves the way for further research on arrhythmia mechanisms in hereditary diseases such as ankyrin-B syndrome.
authors: Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway, m.k.stokke@medisin.uio.no
authors: Mathis Korseberg
authors: MK
authors: Stokke
authors: Frederic
authors: F
authors: Rivelsrud
authors: Ivar
authors: I
authors: Sjaastad
authors: Ole M
authors: OM
authors: Sejersted
authors: Fredrik
authors: F
authors: Swift
mesh_terms: D017487:Ankyrins / Q000235:genetics / Q000502:physiology*; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000502:physiology*; D021962:Membrane Microdomains / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology
chemical_list: C498994:ANK2 protein, human; D017487:Ankyrins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D002118:Calcium