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Intracellular calcium and the mechanism of anodal supernormal excitability in langendorff perfused rabbit ventricles

Authors
 Boyoung Joung ; Hyung-Wook Park ; Peng-Sheng Chen ; Shien-Fong Lin ; James N. Weiss ; Gianfranco Piccirillo ; Seongwook Han ; Juan Song ; Liang Tang ; Mitsunori Maruyama 
Citation
 Circulation Journal, Vol.75(4) : 834~843, 2011 
Journal Title
 Circulation Journal 
ISSN
 1346-9843 
Issue Date
2011
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)). METHODS AND 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
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/93355
DOI
10.1253/circj.CJ-10-1014
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
Yonsei Authors
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