title: Facilitation of L-type calcium currents by diastolic depolarization in cardiac cells: impairment in heart failure.
abstract: OBJECTIVE
  Decay kinetics of the voltage-gated L-type Ca(2+) current (I(CaL)) control the magnitude of Ca(2+) influx during the cardiac action potential. We investigated the influence of changes in diastolic membrane potential on I(CaL) decay kinetics in cardiac cells.
  
  
  METHODS
  Cells were isolated enzymatically from rat ventricles, human right atrial appendages obtained during corrective heart surgery and left ventricles from end-stage failing hearts of transplant recipients. The whole-cell patch-clamp technique was used to evoke I(CaL) by a 100-ms depolarizing test pulse to -10 mV. Conditioning potentials between -80 and 0 mV were applied for 5 s prior to the test pulse.
  
  
  RESULTS
  Depolarizing the cells between -80 and -50 mV prior to the test pulse slowed the early inactivation of I(CaL) both in rat ventricular and human atrial cells. This slowing resulted in a significant increase of Ca(2+) influx. This type of facilitation was not observed when the sarcoplasmic reticulum (SR) Ca(2+) content was depleted using ryanodine which reduced the rate of inactivation of I(CaL), or when Ba(2+) replaced Ca(2+) as the permeating ion. Facilitation was favored by intracellular cAMP-promoting agents that, in addition to increasing current peak amplitude, enhanced the fast Ca(2+)-dependent inactivation of I(CaL). Facilitation was impaired in atrial and ventricular human failing hearts.
  
  
  CONCLUSIONS
  Decay kinetics of I(CaL) are regulated by the diastolic membrane potential in rat and human cardiomyocytes. This regulation, which associates slowing of I(CaL) inactivation with reduced SR Ca(2+) release and underlies facilitation of Ca(2+) channels activity, may have profound physiological relevance for catecholamines enhancement of Ca(2+) influx. It is impaired in failing hearts, possibly due to lowered SR Ca(2+) release.
authors.affiliation: Institut de Génétique Humaine, CNRS, UPR 1142, Montpellier, France.
authors.forename: S
authors.initials: S
authors.lastname: Barrère-Lemaire
authors.forename: C
authors.initials: C
authors.lastname: Piot
authors.forename: F
authors.initials: F
authors.lastname: Leclercq
authors.forename: J
authors.initials: J
authors.lastname: Nargeot
authors.forename: S
authors.initials: S
authors.lastname: Richard
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000818:Animals; D001464:Barium / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003971:Diastole; D004558:Electric Stimulation; D006325:Heart Atria; D006333:Heart Failure / Q000378:metabolism*; D006352:Heart Ventricles; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D011921:Rats, Inbred WKY; D012433:Ryanodine / Q000494:pharmacology; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D012433:Ryanodine; D001464:Barium; D012701:Serotonin; D003994:Bucladesine; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol; D002118:Calcium