Downregulation of the calcium current in human right atrial myocytes from patients in sinus rhythm but with a high risk of atrial fibrillation.
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.
Dinanian
Sylvie
S
Cardiology Department, Hôpital Antoine-Béclère, Assistance Publique-Hôpitaux de Paris, Clamart, France.
Boixel
Christophe
C
Juin
Christophe
C
Hulot
Jean-Sébastien
JS
Coulombe
Alain
A
Rücker-Martin
Catherine
C
Bonnet
Nicolas
N
Le Grand
Bruno
B
Slama
Michel
M
Mercadier
Jean-Jacques
JJ
Hatem
Stéphane N
SN
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
D000318:Adrenergic beta-Agonists; D015415:Biomarkers; D020746:Calcium Channels, L-Type