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

Boyoung Joung, Hyung Wook Park, Mitsunori Maruyama, Liang Tang, Juan Song, Seongwook Han, Gianfranco Piccirillo, James N. Weiss, Shien Fong Lin, Peng Sheng Chen

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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±10 ms) coincided with the -(dCai/dt)max (199±10 ms, 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.

Original languageEnglish
Pages (from-to)834-843
Number of pages10
JournalCirculation Journal
Volume75
Issue number4
DOIs
Publication statusPublished - 2011 Apr 1

Fingerprint

Ventricular Fibrillation
Rabbits
Calcium
Ryanodine
Thapsigargin
Membrane Potentials
Electrodes
Cell Membrane
1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Joung, Boyoung ; Park, Hyung Wook ; Maruyama, Mitsunori ; Tang, Liang ; Song, Juan ; Han, Seongwook ; Piccirillo, Gianfranco ; Weiss, James N. ; Lin, Shien Fong ; Chen, Peng Sheng. / Intracellular calcium and the mechanism of anodal supernormal excitability in langendorff perfused rabbit ventricles. In: Circulation Journal. 2011 ; Vol. 75, No. 4. pp. 834-843.
@article{98b8fb3a92c84c34a6a961236862aaa2,
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 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±10 ms) coincided with the -(dCai/dt)max (199±10 ms, 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.",
author = "Boyoung Joung and Park, {Hyung Wook} and Mitsunori Maruyama and Liang Tang and Juan Song and Seongwook Han and Gianfranco Piccirillo and Weiss, {James N.} and Lin, {Shien Fong} and Chen, {Peng Sheng}",
year = "2011",
month = "4",
day = "1",
doi = "10.1253/circj.CJ-10-1014",
language = "English",
volume = "75",
pages = "834--843",
journal = "Circulation Journal",
issn = "1346-9843",
publisher = "Japanese Circulation Society",
number = "4",

}

Joung, B, Park, HW, Maruyama, M, Tang, L, Song, J, Han, S, Piccirillo, G, Weiss, JN, Lin, SF & Chen, PS 2011, 'Intracellular calcium and the mechanism of anodal supernormal excitability in langendorff perfused rabbit ventricles', Circulation Journal, vol. 75, no. 4, pp. 834-843. https://doi.org/10.1253/circj.CJ-10-1014

Intracellular calcium and the mechanism of anodal supernormal excitability in langendorff perfused rabbit ventricles. / Joung, Boyoung; Park, Hyung Wook; Maruyama, Mitsunori; Tang, Liang; Song, Juan; Han, Seongwook; Piccirillo, Gianfranco; Weiss, James N.; Lin, Shien Fong; Chen, Peng Sheng.

In: Circulation Journal, Vol. 75, No. 4, 01.04.2011, p. 834-843.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intracellular calcium and the mechanism of anodal supernormal excitability in langendorff perfused rabbit ventricles

AU - Joung, Boyoung

AU - Park, Hyung Wook

AU - Maruyama, Mitsunori

AU - Tang, Liang

AU - Song, Juan

AU - Han, Seongwook

AU - Piccirillo, Gianfranco

AU - Weiss, James N.

AU - Lin, Shien Fong

AU - Chen, Peng Sheng

PY - 2011/4/1

Y1 - 2011/4/1

N2 - 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±10 ms) coincided with the -(dCai/dt)max (199±10 ms, 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.

AB - 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±10 ms) coincided with the -(dCai/dt)max (199±10 ms, 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.

UR - http://www.scopus.com/inward/record.url?scp=79953652961&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953652961&partnerID=8YFLogxK

U2 - 10.1253/circj.CJ-10-1014

DO - 10.1253/circj.CJ-10-1014

M3 - Article

C2 - 21301131

AN - SCOPUS:79953652961

VL - 75

SP - 834

EP - 843

JO - Circulation Journal

JF - Circulation Journal

SN - 1346-9843

IS - 4

ER -