title: Intracellular calcium and the mechanism of anodal supernormal excitability in langendorff perfused rabbit ventricles.
abstract: BACKGROUND
  Anodal stimulation hyperpolarizes the cell membrane and increases the intracellular Ca(2+) (Ca(i)) transient. This study tested the hypothesis that the maximum slope of the Ca(i) decline (-(dCa(i)/dt)(max)) corresponds to the timing of anodal dip on the strength-interval curve and the initiation of repetitive responses and ventricular fibrillation (VF) after a premature stimulus (S(2)).
  
  
  RESULTS
  We simultaneously mapped the membrane potential (V(m)) and Ca(i) in 23 rabbit ventricles. A dip in the anodal strength-interval curve was observed. During the anodal dip, ventricles were captured by anodal break excitation directly under the S(2) electrode. The Ca(i) following anodal stimuli is larger than that following cathodal stimuli. The S(1)-S(2) intervals of the anodal dip (203±10 ms) coincided with the -(dCa(i)/dt)(max) (199±10 ms, P=NS). BAPTA-AM (n=3), inhibition of the electrogenic Na(+)-Ca(2+) exchanger current (I(NCX)) by low extracellular Na(+) (n=3), and combined ryanodine and thapsigargin infusion (n=2) eliminated the anodal supernormality. Strong S(2) during the relative refractory period (n=5) induced 29 repetitive responses and 10 VF episodes. The interval between S(2) and the first non-driven beat was coincidental with the time of -(dCa(i)/dt)(max).
  
  
  CONCLUSIONS
  Larger Ca(i) transient and I(NCX) activation induced by anodal stimulation produces anodal supernormality. The time of maximum I(NCX) activation is coincidental to the induction of non-driven beats from the Ca(i) sinkhole after a strong premature stimulation.
authors.affiliation: Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Boyoung
authors.initials: B
authors.lastname: Joung
authors.forename: Hyung-Wook
authors.initials: HW
authors.lastname: Park
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Maruyama
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.forename: Juan
authors.initials: J
authors.lastname: Song
authors.forename: Seongwook
authors.initials: S
authors.lastname: Han
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Piccirillo
authors.forename: James N
authors.initials: JN
authors.lastname: Weiss
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004558:Electric Stimulation / Q000379:methods; D004566:Electrodes; D006352:Heart Ventricles / Q000378:metabolism*; D008564:Membrane Potentials; D010477:Perfusion; D011817:Rabbits
chemical_list: D002118:Calcium