title: Downregulation of the calcium current in human right atrial myocytes from patients in sinus rhythm but with a high risk of atrial fibrillation.
abstract: OBJECTIVE
  A decrease in L-type calcium current (ICaL) is an important mechanism favouring atrial fibrillation (AF). Here, we aimed to identify pathogenic factors associated with ICaL downregulation.
  
  
  RESULTS
  Atrial myocytes were isolated from right atrial appendages obtained from 86 adult patients in sinus rhythm with coronary artery disease, aortic valve disease, or mitral valve disease (MVD). Current was recorded in isolated myocytes using the whole-cell patch-clamp technique. The ICaL recorded in the 172 myocytes studied showed a marked variability of peak density ranging from 0.1 to 9.0 pA/pF. The ICaL peak density did not correlate with membrane capacitance or changes in current biophysical properties. The ICaL peak density was homogeneous for a given sample. Small ICaL values were recorded in patients with MVD or with a low left ventricular ejection fraction (<45%). Small ICaL values were more sensitive to the beta-adrenergic agonist, isoproterenol (1 microM), and to the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (10 microM).
  
  
  CONCLUSIONS
  In human atrial myocytes, the variability of ICaL is related to the clinical history of the donors. The downregulation of ICaL is already observed in patients in sinus rhythm with a high risk of AF and is associated with the greatest response to beta-adrenergic agonist.
authors.affiliation: Cardiology Department, Hôpital Antoine-Béclère, Assistance Publique-Hôpitaux de Paris, Clamart, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dinanian
authors.forename: Christophe
authors.initials: C
authors.lastname: Boixel
authors.forename: Christophe
authors.initials: C
authors.lastname: Juin
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hulot
authors.forename: Alain
authors.initials: A
authors.lastname: Coulombe
authors.forename: Catherine
authors.initials: C
authors.lastname: Rücker-Martin
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bonnet
authors.forename: Bruno
authors.initials: B
authors.lastname: Le Grand
authors.forename: Michel
authors.initials: M
authors.lastname: Slama
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Mercadier
authors.forename: Stéphane N
authors.initials: SN
authors.lastname: Hatem
mesh_terms: D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018570:Risk Assessment
chemical_list: D000318:Adrenergic beta-Agonists; D015415:Biomarkers; D020746:Calcium Channels, L-Type