title: Pacing-induced heart failure causes a reduction of delayed rectifier potassium currents along with decreases in calcium and transient outward currents in rabbit ventricle.
abstract: OBJECTIVE
  Heart failure in patients and in animal models is associated with action potential prolongation of the ventricular myocytes. Changes in several membrane currents have been already demonstrated to underlie this prolongation. However, information on the two components (I(Kr) and I(Ks)) of the delayed rectifier potassium current (I(K)) in rapid pacing induced heart failure is lacking.
  
  
  RESULTS
  Action potentials and whole-cell currents, I(K), I(to1), I(K1), and I(Ca-L) were recorded in apical myocytes of left ventricle from 10 rabbits subjected to left ventricular pacing at 350-380 beats/min for 3-4 weeks and 10 controls with sham operation. Action potential duration at 90% repolarization (APD(90)) was prolonged in myocytes from failing hearts compared to controls at both cycle lengths of 333 and 1000 ms. Both E-4031-sensitive and -resistant components of I(K) (I(Kr), I(Ks)) in myocytes from failing hearts were significantly less than those of control hearts; tail current densities of I(Kr) and I(Ks) following depolarization to +50 mV were 0.62+/-0.05 vs. 0.96+/-0.12 pA/pF (P<0.05), and 0.27+/-0.08 vs. 0.52+/-0.08 pA/pF (P<0.05), respectively. There was no significant difference between control and failing myocytes in the voltage- and time-dependence of activation of total I(K), I(Kr) and I(Ks). The peak of L-type Ca(2+) current (I(Ca-L)) was significantly reduced in myocytes from failing hearts (at +10 mV, -9.29+/-0.52 vs. -12.28+/-1.63 pA/pF, P<0.05), as was the Ca(2+)-independent transient outward current (I(to1); at +40 mV, 4.8+/-0.9 vs. 9.6+/-1.3 pA/pF, P<0.05). Steady state I-V curve for I(K1) was similar in myocytes from failing and control hearts.
  
  
  CONCLUSIONS
  Decrease of I(K) (both I(Kr) and I(Ks)) in addition to reduced I(to1), may underly action potential prolongation at physiological cycle length and thereby contribute to arrhythmogenesis in heart failure.
authors.affiliation: Department of Circulation, Division of Regulation of Organ Function, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuji
authors.forename: T
authors.initials: T
authors.lastname: Opthof
authors.forename: K
authors.initials: K
authors.lastname: Kamiya
authors.forename: K
authors.initials: K
authors.lastname: Yasui
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.forename: I
authors.initials: I
authors.lastname: Kodama
mesh_terms: D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002304:Cardiac Pacing, Artificial; D006333:Heart Failure / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits
chemical_list: D000889:Anti-Arrhythmia Agents; D020746:Calcium Channels, L-Type; D010880:Piperidines; D015221:Potassium Channels; D011725:Pyridines; C063968:E 4031