title: Ca2+ current-mediated regulation of action potential by pacing rate in rat ventricular myocytes.
abstract: 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).
authors.affiliation: INSERM U-390, Physiopathologie Cardiovasculaire, CHU Arnaud de Villeneuve, Montpellier, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Fauconnier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bedut
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Le Guennec
authors.forename: Dominique
authors.initials: D
authors.lastname: Babuty
authors.forename: Sylvain
authors.initials: S
authors.lastname: Richard
mesh_terms: 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
chemical_list: D020746:Calcium Channels, L-Type; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012433:Ryanodine; D019284:Thapsigargin; D015761:4-Aminopyridine