| Autor: |
Mangoni, Matteo E., Fontanaud, Pierre, Noble, Penelope J., Noble, Denis, Benkemoun, Henri, Nargeot, Joël, Richard, Sylvain |
| Zdroj: |
Cardiovascular Research; 2000, Vol. 48 Issue 3, p375-392, 18p |
| Abstrakt: |
Objective: The L-type Ca2+ current (ICa,L) contributes to the generation and modulation of the pacemaker action potential (AP). We investigated facilitation of ICa,L in sino-atrial cells. Methods: Facilitation was studied in regularly-beating cells isolated enzymatically from young albino rabbits (0.8–1 kg). We used the whole-cell patch-clamp technique to vary the frequency of the test depolarizations evoked at −10 mV or the conditioning diastolic membrane potential prior to the test pulse. Results: High frequencies (range 0.2–3.5 Hz) slowed the decay kinetics of ICa,L evoked from a holding potential (HP) of −80 mV in 68% of cells resulting in a larger Ca2+ influx during the test pulse. The amount of facilitation increased progressively between 0.2 and 3.0 Hz. When the frequency was changed from 0.1 to 1 Hz, the averaged increase in the time integral of ICa,L was 27±7% (n = 22). Application of conditioning voltages between −80 and −50 mV induced similar facilitation of ICa,L in 73% of cells. The maximal increase of Ca2+ entry occurred between −60 and −50 mV, and was on average 38±14% for conditioning prepulses of 5 s in duration (n = 15). Numerical simulations of the pacemaker activity showed that facilitation of ICa,L promotes stability of sino-atrial rate by enhancing Ca2+ entry, thus establishing a negative feedback control against excessive heart rate slowing. Conclusion: Facilitation of ICa,L is present in rabbit sino-atrial cells. The underlying mechanism reflects modulation of ICa,L decay kinetics by diastolic membrane potential and frequency of depolarization. This phenomenon may provide an important regulatory mechanism of sino-atrial automaticity. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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