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+ curr ents of the patients' medication and of the duration of AF. Methods and res ults. Human atrial myocytes were prepared from the right auricles of patien ts undergoing open-heart surgery. Three groups of patients were studied: a control group with sinus rhythm (SR, n = 26 patients) and a group with pers istent 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-ty pe Ca2+ currents were measured during depolarizing pulses from a holding po tential of-70 mV to a test potential of +10 mV and are given as mean +/- SE M of current densities (currents normalized to the cell capacitance). Ca2current densities were significantly (p < 0.0001) smaller in cells from pat ients with persistent AF than in control cells (0.54 <plus/minus> 0.08 pA/p F 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 digi talis. Stimulation with the dihydropyridine Bay K 8644 (1 muM) or with isop roterenol (0.1 muM) increased Ca2+ currents in control cells 3.5 +/- 0.2 an d 3.5 +/- 0.3-fold. In persistent AF, this increase was significantly large r (6.0 +/- 0.5 and 5.2 +/- 0.6-fold) but stimulated currents were still sig nificantly lower than in control cells. Patients with non-persistent AF exh ibited Ca2+ currents well within the control range. Conclusion. 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 par t of the myocardial remodeling during long-lasting atrial fibrillation. It is not present in patients with non-persistent AF and not caused by medicat ion.