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L-type calcium currents in atrial myocytes from patients with persistent and non-persistent atrial fibrillation
1Institut für Physiologie, Universitätsklinikum der RWTH Aachen.
Insights
Persistent atrial fibrillation (AF) significantly reduces L-type calcium currents in heart cells, impacting myocardial function. This reduction is not due to medication and is absent in non-persistent AF.
Area of Science:
- Cardiology
- Electrophysiology
- Molecular Cardiology
Background:
- Persistent atrial fibrillation (AF) is associated with impaired atrial contractility and altered action potential characteristics.
- A reduction in L-type calcium currents has been recently observed in patients with persistent AF.
Purpose of the Study:
- To investigate the effects of AF duration and patient medication on L-type calcium currents in atrial myocytes.
- To determine the pathophysiological role of altered calcium currents in atrial remodeling during AF.
Main Methods:
- Human atrial myocytes were isolated from patients with persistent AF, non-persistent AF, and sinus rhythm (controls).
- L-type calcium currents were measured using electrophysiological techniques.
- The impact of medications (calcium channel blockers, beta-blockers, digitalis) and stimulatory agents (Bay K 8644, isoproterenol) on calcium currents was assessed.
Main Results:
- Calcium current densities were significantly lower in patients with persistent AF compared to controls (p < 0.0001).
- Medications did not account for the observed reduction in calcium currents.
- While stimulatory agents increased calcium currents in AF patients, the levels remained lower than in controls.
- Patients with non-persistent AF showed calcium currents within the normal range.
Conclusions:
- Reduced L-type calcium currents are a characteristic feature of myocardial remodeling in persistent AF.
- This reduction is attributed to both a decreased number and function of L-type channels.
- The observed changes are specific to long-standing AF and are independent of patient medication.
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.
Methods And 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.
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 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.