Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Intracellular Calcium and the Mechanism of Anodal Supernormal Excitability in Langendorff Perfused Rabbit Ventricles
Boyoung JoungHyung-Wook ParkMitsunori MaruyamaLiang TangJuan SongSeongwook HanGianfranco PiccirilloJames N. WeissShien-Fong LinPeng-Sheng Chen
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2011 Volume 75 Issue 4 Pages 834-843


Background: Anodal stimulation hyperpolarizes the cell membrane and increases the intracellular Ca2+ (Cai) transient. This study tested the hypothesis that the maximum slope of the Cai decline (-(dCai/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 (S2). Methods and Results: We simultaneously mapped the membrane potential (Vm) and Cai 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 S2 electrode. The Cai following anodal stimuli is larger than that following cathodal stimuli. The S1-S2 intervals of the anodal dip (203±10ms) coincided with the -(dCai/dt)max (199±10ms, P=NS). BAPTA-AM (n=3), inhibition of the electrogenic Na+-Ca2+ exchanger current (INCX) by low extracellular Na+ (n=3), and combined ryanodine and thapsigargin infusion (n=2) eliminated the anodal supernormality. Strong S2 during the relative refractory period (n=5) induced 29 repetitive responses and 10 VF episodes. The interval between S2 and the first non-driven beat was coincidental with the time of -(dCai/dt)max. Conclusions: Larger Cai transient and INCX activation induced by anodal stimulation produces anodal supernormality. The time of maximum INCX activation is coincidental to the induction of non-driven beats from the Cai sinkhole after a strong premature stimulation. (Circ J 2011; 75: 834-843)

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