© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Facilitation of the L-type calcium current in rabbit sino-atrial cells: effect on cardiac automaticity
aUPR 1142 CNRS, Institut de Génétique Humaine, 141 rue de la Cardonille, Montpellier Cedex 5, France
bUMR 5101 CNRS, 141 rue de la Cardonille, Montpellier Cedex 5, France
cUniversity Laboratory of Physiology, Parks Road OX1 3 PT, UK
* Corresponding author. Tel.: +33-499-619-939; fax: +33-499-619-901 srichard{at}igh.cnrs.fr
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.
KEYWORDS Ca-channel; Impulse formation; Sinus node
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Alig, L. Marger, P. Mesirca, H. Ehmke, M. E. Mangoni, and D. Isbrandt Control of heart rate by cAMP sensitivity of HCN channels PNAS, July 21, 2009; 106(29): 12189 - 12194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Maltsev and E. G. Lakatta Synergism of coupled subsarcolemmal Ca2+ clocks and sarcolemmal voltage clocks confers robust and flexible pacemaker function in a novel pacemaker cell model Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H594 - H615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Mangoni and J. Nargeot Genesis and Regulation of the Heart Automaticity Physiol Rev, July 1, 2008; 88(3): 919 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Maltsev and E. G. Lakatta Dynamic interactions of an intracellular Ca2+ clock and membrane ion channel clock underlie robust initiation and regulation of cardiac pacemaker function Cardiovasc Res, January 18, 2008; (2008) cvm058v3. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Fauconnier, A. Lacampagne, J.-M. Rauzier, P. Fontanaud, J.-M. Frapier, O. M. Sejersted, G. Vassort, and S. Richard Frequency-dependent and proarrhythmogenic effects of FK-506 in rat ventricular cells Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H778 - H786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Gomez and S. Richard Mutant cardiac ryanodine receptors and ventricular arrhythmias: is 'gain-of-function' obligatory? Cardiovasc Res, October 1, 2004; 64(1): 3 - 5. [Full Text] [PDF]
|
|
|
|
 |
|
 J Guo and H J Duff Inactivation of ICa-L is the major determinant of use-dependent facilitation in rat cardiomyocytes J. Physiol., March 15, 2003; 547(3): 797 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kurata, I. Hisatome, S. Imanishi, and T. Shibamoto Dynamical description of sinoatrial node pacemaking: improved mathematical model for primary pacemaker cell Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H2074 - H2101. [Abstract] [Full Text] [PDF]
|
|