L-type calcium currents in atrial myocytes from patients with persistent and non-persistent atrial fibrillation.
OBJECTIVE
In patients with persistent atrial fibrillation (AF), the atrial myocardium is characterized by a reduced contractile force, by a shortened duration of the action potential and a recently demonstrated reduction of the L-type Ca2+ currents. We analyzed potential effects on L-type Ca2+ currents of the patients' medication and of the duration of AF.


RESULTS
Human atrial myocytes were prepared from the right auricles of patients undergoing open-heart surgery. Three groups of patients were studied: a control group with sinus rhythm (SR, n = 26 patients) and a group with persistent AF (> 3 months duration; n = 10), a group with non-persistent AF (3 patients with SR but with documented episodes of AF in their history). L-type Ca2+ currents were measured during depolarizing pulses from a holding potential of -70 mV to a test potential of +10 mV and are given as mean +/- SEM of current densities (currents normalized to the cell capacitance). Ca2+ current densities were significantly (p < 0.0001) smaller in cells from patients with persistent AF than in control cells (0.54 +/- 0.08 pA/pF vs. 1.96 +/- 0.12 pA/pF). No indication was found that these changes were caused by medication with Ca2+ channel antagonists, beta blockers, or digitalis. Stimulation with the dihydropyridine Bay K 8644 (1 microM) or with isoproterenol (0.1 microM) increased Ca2+ currents in control cells 3.5 +/- 0.2 and 3.5 +/- 0.3-fold. In persistent AF, this increase was significantly larger (6.0 +/- 0.5 and 5.2 +/- 0.6-fold) but stimulated currents were still significantly lower than in control cells. Patients with non-persistent AF exhibited Ca2+ currents well within the control range.


CONCLUSIONS
A reduction in Ca2+ currents, due to a reduction in number as well as a depression of L-type channels, is a characteristic and pathophysiologically important part of the myocardial remodeling during long-lasting atrial fibrillation. It is not present in patients with non-persistent AF and not caused by medication.
Skasa
M
M
Institut für Physiologie, Universitätsklinikum der RWTH Aachen.
Jüngling
E
E
Picht
E
E
Schöndube
F
F
Lückhoff
A
A
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000378:metabolism* / Q000503:physiopathology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D012008:Recurrence
D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D007545:Isoproterenol