Ca2+ current-mediated regulation of action potential by pacing rate in rat ventricular myocytes.
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.


CONCLUSIONS
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).
Fauconnier
Jérémy
J
INSERM U-390, Physiopathologie Cardiovasculaire, CHU Arnaud de Villeneuve, Montpellier, France.
Bedut
Stéphane
S
Le Guennec
Jean-Yves
JY
Babuty
Dominique
D
Richard
Sylvain
S
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002478:Cells, Cultured; D046508:Culture Techniques; D006321:Heart / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology; D032342:Muscle Cells / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D011921:Rats, Inbred WKY; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D019284:Thapsigargin / Q000494:pharmacology; D016276:Ventricular Function
D020746:Calcium Channels, L-Type; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012433:Ryanodine; D019284:Thapsigargin; D015761:4-Aminopyridine