Role of sarcoplasmic reticulum calcium in development of secondary calcium rise and early afterdepolarizations in long QT syndrome rabbit model

Po Cheng Chang, Hung Ta Wo, Hui Ling Lee, Shien-Fong Lin, Ming Shien Wen, Yen Chu, San Jou Yeh, Chung Chuan Chou

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: L-type calcium current reactivation plays an important role in development of early afterdepolarizations (EADs) and torsades de pointes (TdP). Secondary intracellular calcium (Cai) rise is associated with initiation of EADs. Objective: To test whether inhibition of sarcoplasmic reticulum (SR) Ca2+ cycling suppresses secondary Cai rise and genesis of EADs. Methods: Langendorff perfusion and dual voltage and Cai optical mapping were conducted in 10 rabbit hearts. Atrioventricular block (AVB) was created by radiofrequency ablation. After baseline studies, E4031, SR Ca2+ cycling inhibitors (ryanodine plus thapsigargin) and nifedipine were then administrated subsequently, and the protocols were repeated. Results: At baseline, there was no spontaneous or pacing-induced TdP. After E4031 administration, action potential duration (APD) was significantly prolonged and the amplitude of secondary Cai rise was enhanced, and 7 (70%) rabbits developed spontaneous or pacing-induced TdP. In the presence of ryanodine plus thapsigargin, TdP inducibility was significantly reduced (2 hearts, 20%, p = 0.03). Although APD was significantly prolonged (from 298 ± 30 ms to 457 ± 75 ms at pacing cycle length of 1000 m, p = 0.007) by ryanodine plus thapsigargin, the secondary Cai rise was suppressed (from 8.8 ± 2.6%to 1.2 ± 0.9%, p = 0.02). Nifedipine inhibited TdP inducibility in all rabbit hearts. Conclusion: In this AVB and long QT rabbit model, inhibition of SR Ca2+ cycyling reduces the inducibility of TdP. The mechanism might be suppression of secondary Cai rise and genesis of EADs.

Original languageEnglish (US)
Article numbere0123868
JournalPLoS One
Volume10
Issue number4
DOIs
StatePublished - Apr 13 2015
Externally publishedYes

Fingerprint

Long QT Syndrome
sarcoplasmic reticulum
Torsades de Pointes
Sarcoplasmic Reticulum
rabbits
Rabbits
Calcium
calcium
Ryanodine
Thapsigargin
Atrioventricular Block
Nifedipine
Action Potentials
heart
action potentials
Ablation
duration
Perfusion
early development
Electric potential

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Role of sarcoplasmic reticulum calcium in development of secondary calcium rise and early afterdepolarizations in long QT syndrome rabbit model. / Chang, Po Cheng; Wo, Hung Ta; Lee, Hui Ling; Lin, Shien-Fong; Wen, Ming Shien; Chu, Yen; Yeh, San Jou; Chou, Chung Chuan.

In: PLoS One, Vol. 10, No. 4, e0123868, 13.04.2015.

Research output: Contribution to journalArticle

Chang, Po Cheng ; Wo, Hung Ta ; Lee, Hui Ling ; Lin, Shien-Fong ; Wen, Ming Shien ; Chu, Yen ; Yeh, San Jou ; Chou, Chung Chuan. / Role of sarcoplasmic reticulum calcium in development of secondary calcium rise and early afterdepolarizations in long QT syndrome rabbit model. In: PLoS One. 2015 ; Vol. 10, No. 4.
@article{37e52c39399549c6ab22530bcb542924,
title = "Role of sarcoplasmic reticulum calcium in development of secondary calcium rise and early afterdepolarizations in long QT syndrome rabbit model",
abstract = "Background: L-type calcium current reactivation plays an important role in development of early afterdepolarizations (EADs) and torsades de pointes (TdP). Secondary intracellular calcium (Cai) rise is associated with initiation of EADs. Objective: To test whether inhibition of sarcoplasmic reticulum (SR) Ca2+ cycling suppresses secondary Cai rise and genesis of EADs. Methods: Langendorff perfusion and dual voltage and Cai optical mapping were conducted in 10 rabbit hearts. Atrioventricular block (AVB) was created by radiofrequency ablation. After baseline studies, E4031, SR Ca2+ cycling inhibitors (ryanodine plus thapsigargin) and nifedipine were then administrated subsequently, and the protocols were repeated. Results: At baseline, there was no spontaneous or pacing-induced TdP. After E4031 administration, action potential duration (APD) was significantly prolonged and the amplitude of secondary Cai rise was enhanced, and 7 (70{\%}) rabbits developed spontaneous or pacing-induced TdP. In the presence of ryanodine plus thapsigargin, TdP inducibility was significantly reduced (2 hearts, 20{\%}, p = 0.03). Although APD was significantly prolonged (from 298 ± 30 ms to 457 ± 75 ms at pacing cycle length of 1000 m, p = 0.007) by ryanodine plus thapsigargin, the secondary Cai rise was suppressed (from 8.8 ± 2.6{\%}to 1.2 ± 0.9{\%}, p = 0.02). Nifedipine inhibited TdP inducibility in all rabbit hearts. Conclusion: In this AVB and long QT rabbit model, inhibition of SR Ca2+ cycyling reduces the inducibility of TdP. The mechanism might be suppression of secondary Cai rise and genesis of EADs.",
author = "Chang, {Po Cheng} and Wo, {Hung Ta} and Lee, {Hui Ling} and Shien-Fong Lin and Wen, {Ming Shien} and Yen Chu and Yeh, {San Jou} and Chou, {Chung Chuan}",
year = "2015",
month = "4",
day = "13",
doi = "10.1371/journal.pone.0123868",
language = "English (US)",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

TY - JOUR

T1 - Role of sarcoplasmic reticulum calcium in development of secondary calcium rise and early afterdepolarizations in long QT syndrome rabbit model

AU - Chang, Po Cheng

AU - Wo, Hung Ta

AU - Lee, Hui Ling

AU - Lin, Shien-Fong

AU - Wen, Ming Shien

AU - Chu, Yen

AU - Yeh, San Jou

AU - Chou, Chung Chuan

PY - 2015/4/13

Y1 - 2015/4/13

N2 - Background: L-type calcium current reactivation plays an important role in development of early afterdepolarizations (EADs) and torsades de pointes (TdP). Secondary intracellular calcium (Cai) rise is associated with initiation of EADs. Objective: To test whether inhibition of sarcoplasmic reticulum (SR) Ca2+ cycling suppresses secondary Cai rise and genesis of EADs. Methods: Langendorff perfusion and dual voltage and Cai optical mapping were conducted in 10 rabbit hearts. Atrioventricular block (AVB) was created by radiofrequency ablation. After baseline studies, E4031, SR Ca2+ cycling inhibitors (ryanodine plus thapsigargin) and nifedipine were then administrated subsequently, and the protocols were repeated. Results: At baseline, there was no spontaneous or pacing-induced TdP. After E4031 administration, action potential duration (APD) was significantly prolonged and the amplitude of secondary Cai rise was enhanced, and 7 (70%) rabbits developed spontaneous or pacing-induced TdP. In the presence of ryanodine plus thapsigargin, TdP inducibility was significantly reduced (2 hearts, 20%, p = 0.03). Although APD was significantly prolonged (from 298 ± 30 ms to 457 ± 75 ms at pacing cycle length of 1000 m, p = 0.007) by ryanodine plus thapsigargin, the secondary Cai rise was suppressed (from 8.8 ± 2.6%to 1.2 ± 0.9%, p = 0.02). Nifedipine inhibited TdP inducibility in all rabbit hearts. Conclusion: In this AVB and long QT rabbit model, inhibition of SR Ca2+ cycyling reduces the inducibility of TdP. The mechanism might be suppression of secondary Cai rise and genesis of EADs.

AB - Background: L-type calcium current reactivation plays an important role in development of early afterdepolarizations (EADs) and torsades de pointes (TdP). Secondary intracellular calcium (Cai) rise is associated with initiation of EADs. Objective: To test whether inhibition of sarcoplasmic reticulum (SR) Ca2+ cycling suppresses secondary Cai rise and genesis of EADs. Methods: Langendorff perfusion and dual voltage and Cai optical mapping were conducted in 10 rabbit hearts. Atrioventricular block (AVB) was created by radiofrequency ablation. After baseline studies, E4031, SR Ca2+ cycling inhibitors (ryanodine plus thapsigargin) and nifedipine were then administrated subsequently, and the protocols were repeated. Results: At baseline, there was no spontaneous or pacing-induced TdP. After E4031 administration, action potential duration (APD) was significantly prolonged and the amplitude of secondary Cai rise was enhanced, and 7 (70%) rabbits developed spontaneous or pacing-induced TdP. In the presence of ryanodine plus thapsigargin, TdP inducibility was significantly reduced (2 hearts, 20%, p = 0.03). Although APD was significantly prolonged (from 298 ± 30 ms to 457 ± 75 ms at pacing cycle length of 1000 m, p = 0.007) by ryanodine plus thapsigargin, the secondary Cai rise was suppressed (from 8.8 ± 2.6%to 1.2 ± 0.9%, p = 0.02). Nifedipine inhibited TdP inducibility in all rabbit hearts. Conclusion: In this AVB and long QT rabbit model, inhibition of SR Ca2+ cycyling reduces the inducibility of TdP. The mechanism might be suppression of secondary Cai rise and genesis of EADs.

UR - http://www.scopus.com/inward/record.url?scp=84929493758&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929493758&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0123868

DO - 10.1371/journal.pone.0123868

M3 - Article

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 4

M1 - e0123868

ER -