title: [Up-regulation of inositol 1, 4, 5-trisphosphate receptor expression in atrial tissue in patients with chronic atrial fibrillation].
abstract: BACKGROUND
  Abnormal intracellular Ca2+ homeostasis occurs in chronic atrial fibrillation(AF). The intracellular Ca2+ concentration is regulated by ryanodine and inositol 1,4,5-trisphosphate (IP3) receptors. Changes occur in ryanodine receptors in atrial tissue from patients in chronic AF. Whether AF patients have alterations in atrial IP3 receptors was investigated.
  
  
  METHODS
  IP3 receptor expression was analyzed in the right atrial myocardium from 13 mitral valvular disease (MVD) patients with AF (MVD/AF), 5MVD patients with normal sinus rhythm(MVD/NSR), and 8 control patients with NSR(tissue obtained during coronary artery bypass surgery). Hemodynamic and echocardiographic data were obtained preoperatively, and an immunohistochemical study was performed on the atrial tissue.
  
  
  RESULTS
  The relative expression level of IP3 receptor protein was significantly greater in MVD/AF (0.75 +/- 0.26) than in MVD/NSR (0.42 +/- 0.13, p < 0.01), and both were significantly above the control value (0.14 +/- 0.08). The relative expression level of IP3 receptor mRNA was significantly greater in MVD/AF(0.028 +/- 0.008) than in control subjects (0.015 +/- 0.004, p < 0.01), but MVD/AF patients did not differ from MVD/NSR (0.020 +/- 0.006) patients. The relative expression levels of IP3 receptor protein and mRNA were higher in patients with left atrial dimension > or = 40 mm, pulmonary capillary wedge pressure > or = 10 mmHg, and right atrial pressure > or = 5 mmHg. IP3 receptors were overexpressed in the cytosol and at the nuclear envelope of atrial myocytes in MVD.
  
  
  CONCLUSIONS
  Since chronic mechanical overload of the atrial myocardium increases IP3 receptor expression, especially in patients with chronic AF, up-regulation of IP3 receptors may be important in modulating intracellular Ca2+ homeostasis and initiating and/or perpetuating AF.
authors.affiliation: Second Department of Internal Medicine, Yamaguchi University, School of Medicine, Minamikogushi 1-1-1, Ube, Yamaguchi 755-8505.
authors.forename: Jutaro
authors.initials: J
authors.lastname: Yamada
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohkusa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nao
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ueyama
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yano
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Hamano
authors.forename: Kensuke
authors.initials: K
authors.lastname: Esato
authors.forename: Masunori
authors.initials: M
authors.lastname: Matsuzaki
mesh_terms: D001281:Atrial Fibrillation / Q000378:metabolism* / Q000503:physiopathology; D015220:Calcium Channels / Q000096:biosynthesis* / Q000378:metabolism; D002908:Chronic Disease; D006325:Heart Atria / Q000378:metabolism*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear