| 12618229 |
Fauconnier J, Bedut S, Le Guennec JY, Babuty D, Richard S: Ca2+ current-mediated regulation of action potential by pacing rate in rat ventricular myocytes. Cardiovasc Res. 2003 Mar;57(3):670-80.
OBJECTIVE: Pacing rate regulates the duration of the cardiac action potential (AP). It also regulates the decay kinetics of the L-type Ca (2+) current (I (Ca-L)) which occurs via modulation of Ca (2+)-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 (approximately 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 Ca (2+). It was antagonised by Ca (2+) channel blockers (Co (2+), 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-Ca (2+) function. CONCLUSION: I (Ca-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-Ca (2+) release and occurs through beat-to-beat adaptation of Ca (2+)-dependent inactivation of I (Ca-L). |
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