| Abstract
| - Abstract. 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.
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