European Heart Journal Advance Access published online on April 7, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn140
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Downregulation of the calcium current in human right atrial myocytes from patients in sinus rhythm but with a high risk of atrial fibrillation
1 Cardiology Department, Hôpital Antoine-Béclère, Assistance Publique-Hôpitaux de Paris, Clamart, France
2 Inserm, UMRS621, Faculté Pierre-Marie Curie, 91 boulevard de lHôpital, 75013 Paris, France
3 Université Pierre et Marie Curie-Paris 6, UMRS621, Paris, France
4 CNRS-UMR-8162, Université Paris-XI, Hopital Marie-Lannelongue, Le-Plessis-Robinson, France
5 Institut de Cardiologie, Hôpital Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France
6 Centre de Recherche Pierre-Fabre, Castres, France
7 Inserm, UMRS698, Paris, France
8 Université Paris-Diderot, Paris, France
9 Department of Physiology, Groupe Hospitalier Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France
10 Department of Cardiology, Groupe Hospitalier Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France
Received 11 August 2007; revised 25 February 2008; accepted 13 March 2008.
* Corresponding author. Tel: +33 1 40 77 95 84, Fax: +33 1 40 77 98 72. Email: stephane.hatem{at}chups.jussieu.fr
Aims: 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.
Methods and 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 β-adrenergic agonist, isoproterenol (1 µM), and to the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (10 µM).
Conclusion: 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 β-adrenergic agonist.
Key Words: Atrial dilatation Atrial fibrillation Calcium current Atrial myocytes Catecholamine
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