© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Ca2+ current-mediated regulation of action potential by pacing rate in rat ventricular myocytes
aINSERM U-390, Physiopathologie Cardiovasculaire, CHU Arnaud de Villeneuve, 34295 Montpellier Cedex 5, France
bCNRS UMR 6542, Faculté des Sciences, Parc de Grandmont, 37200 Tours, France
cINSERM Emi-U 0211 N2C, Faculté de Médecine, 2 Boulevard Tonnellé, 37032 Tours, France
srichard{at}montp.inserm.fr
* Corresponding author. Tel.: +33-4-6741-5244; fax: +33-4-6741-5242.
Objective: Pacing rate regulates the duration of the cardiac action potential (AP). It also regulates the decay kinetics of the L-type Ca2+ current (ICa-L) which occurs via modulation of Ca2+-dependent inactivation. We investigated whether and how this latter process contributes to frequency-dependent (FD) changes in the AP waveform in rat ventricular cells. Methods: We recorded APs using a microelectrode technique in rat papillary muscles, and using the whole-cell current patch-clamp technique in single rat ventricular cells. Results: The AP duration (APD) was increased by high rates encompassing the physiological range (0.1–5.7 Hz) in both papillary muscles and single cells. This prolongation was accompanied by concomitant depolarisation (
7 mV at 5.7 Hz) of the membrane potential (MP) in papillary muscles. Equivalent artificial depolarisation of the MP enhanced the FD prolongation in single cells. The FD prolongation was enhanced in presence of the K+ current blocker 4-aminopyridine (5 mmol/l), and decreased in absence of extracellular Ca2+. It was antagonised by Ca2+ channel blockers (Co2+, nifedipine, nitrendipine) and decreased by use of high EGTA (10 vs. 0.5 mmol/l EGTA) or BAPTA (20 mmol/l) in the patch-pipette. It was prevented by ryanodine or thapsigargin, two drugs that reduce or abolish SR-Ca2+ function. Conclusion: ICa-L contributes to the FD modulation of the AP, which occurs following a sudden change in cardiac frequency in rat ventricular cells. This highly dynamic physiological process is related to SR-Ca2+ release and occurs through beat-to-beat adaptation of Ca2+-dependent inactivation of ICa-L.
KEYWORDS Ca channel; Calcium (cellular); Heart rate (variability); Membrane potential; SR (function)
1 Both authors contributed equally to this work.
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