title: Facilitation of the L-type calcium current in rabbit sino-atrial cells: effect on cardiac automaticity.
abstract: OBJECTIVE
  The L-type Ca(2+) current (I(Ca,L)) contributes to the generation and modulation of the pacemaker action potential (AP). We investigated facilitation of I(Ca,L) in sino-atrial cells.
  
  
  METHODS
  Facilitation was studied in regularly-beating cells isolated enzymatically from young albino rabbits (0.8-1 kg). We used the whole-cell patch-clamp technique to vary the frequency of the test depolarizations evoked at -10 mV or the conditioning diastolic membrane potential prior to the test pulse.
  
  
  RESULTS
  High frequencies (range 0.2-3.5 Hz) slowed the decay kinetics of I(Ca,L) evoked from a holding potential (HP) of -80 mV in 68% of cells resulting in a larger Ca(2+) influx during the test pulse. The amount of facilitation increased progressively between 0.2 and 3.0 Hz. When the frequency was changed from 0.1 to 1 Hz, the averaged increase in the time integral of I(Ca,L) was 27+/-7% (n=22). Application of conditioning voltages between -80 and -50 mV induced similar facilitation of I(Ca,L) in 73% of cells. The maximal increase of Ca(2+) entry occurred between -60 and -50 mV, and was on average 38+/-14% for conditioning prepulses of 5 s in duration (n=15). Numerical simulations of the pacemaker activity showed that facilitation of I(Ca,L) promotes stability of sino-atrial rate by enhancing Ca(2+) entry, thus establishing a negative feedback control against excessive heart rate slowing.
  
  
  CONCLUSIONS
  Facilitation of I(Ca,L) is present in rabbit sino-atrial cells. The underlying mechanism reflects modulation of I(Ca,L) decay kinetics by diastolic membrane potential and frequency of depolarization. This phenomenon may provide an important regulatory mechanism of sino-atrial automaticity.
authors.affiliation: UPR 1142 CNRS, Institut de Génétique Humaine, 141 rue de la Cardonille, Cedex 5, Montpellier, France.
authors.forename: M E
authors.initials: ME
authors.lastname: Mangoni
authors.forename: P
authors.initials: P
authors.lastname: Fontanaud
authors.forename: P J
authors.initials: PJ
authors.lastname: Noble
authors.forename: D
authors.initials: D
authors.lastname: Noble
authors.forename: H
authors.initials: H
authors.lastname: Benkemoun
authors.forename: J
authors.initials: J
authors.lastname: Nargeot
authors.forename: S
authors.initials: S
authors.lastname: Richard
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D003198:Computer Simulation; D004558:Electric Stimulation; D005110:Extracellular Space / Q000378:metabolism; D005246:Feedback; D008564:Membrane Potentials / Q000502:physiology; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D012849:Sinoatrial Node / Q000378:metabolism*
chemical_list: D020746:Calcium Channels, L-Type; D002118:Calcium