title: Ionic remodeling of cardiac Purkinje cells by congestive heart failure.
abstract: BACKGROUND
  Cardiac Purkinje cells (PCs) are important for the generation of triggered arrhythmias, particularly in association with abnormal repolarization. The effects of congestive heart failure (CHF) on the ionic properties of PCs are unknown.
  
  
  RESULTS
  PCs were isolated from false tendons of control dogs and dogs with ventricular tachypacing-induced CHF. CHF PCs were hypertrophied (capacitance, mean+/-SEM, 149+/-4 pF, n=130; versus 128+/-3 pF, n=150, control; P<0.001). Transient outward current density was reduced in CHF PCs without change in voltage dependence or kinetics. CHF also reduced inward-rectifier current density, with no change in form of the current-voltage relationship. Densities of L- and T-type calcium, rapid and slow delayed rectifier, and Na(+)-Ca(2+) exchange currents were unaltered by CHF, but L-type calcium current inactivation was slowed at positive potentials. Purkinje fiber action potentials from CHF dogs showed decreased phase 1 amplitudes and elevated plateau voltages and demonstrated twice as much prolongation on exposure to the rapid delayed rectifier blocker E-4031 as control Purkinje fibers.
  
  
  CONCLUSIONS
  CHF causes remodeling of important K(+) and Ca(2+) currents in cardiac PCs, decreasing repolarization reserve and causing an exaggerated repolarization delay in response to a class III drug. These results have important potential implications regarding ventricular arrhythmogenesis, particularly related to triggered activity in PCs, in patients with CHF.
authors.affiliation: Department of Medicine, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Han
authors.forename: D
authors.initials: D
authors.lastname: Chartier
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Nattel
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
chemical_list: D000889:Anti-Arrhythmia Agents; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D010880:Piperidines; D015221:Potassium Channels; D011725:Pyridines; D019831:Sodium-Calcium Exchanger; C063968:E 4031; D001464:Barium; D012964:Sodium; D011188:Potassium; D002118:Calcium