Aging increases pulmonary veins arrhythmogenesis and susceptibility to calcium regulation agents

Wanwarang Wongcharoen, Yao Chang Chen, Yi Jen Chen, Szu Ying Chen, Huang I. Yeh, Cheng I. Lin, Shih Ann Chen

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background: Aging and pulmonary veins (PVs) play a critical role in the pathophysiology of atrial fibrillation. Abnormal Ca2+ regulation and ryanodine receptors are known to contribute to PV arrhythmogenesis. Objective: The purpose of this study was to investigate whether aging alters PV electrophysiology, Ca2+ regulation proteins, and responses to rapamycin, FK-506, ryanodine, and ouabain. Methods: Conventional microelectrodes were used to record action potential and contractility in isolated PV tissue samples in 15 young (age 3 months) and 16 aged (age 3 years) rabbits before and after drug administration. Expression of sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), ryanodine receptor, and Na+/Ca2+ exchanger was evaluated by western blot. Results: Aged PVs had larger amplitude of delayed afterdepolarizations, greater depolarized resting membrane potential, longer action potential duration, and higher incidence of action potential alternans and contractile alternans with increased expression of Na+/Ca2+ exchanger and ryanodine receptor and decreased expression of SERCA2a. Rapamycin (1,10,100 nM), FK-506 (0.01, 0.1, 1 μM), ryanodine (0.1, 1 μM), and ouabain (0.1, 1 μM) concentration-dependently increased PV spontaneous rates and the incidence of delayed afterdepolarizations in young and aged PVs. Compared with results in young PVs, rapamycin and FK-506 in aged PVs increased PV spontaneous rates to a greater extent and exhibited a larger delayed afterdepolarization amplitude. In PVs without spontaneous activity, rapamycin and FK-506 induced spontaneous activity only in aged PVs, but ryanodine and ouabain induced spontaneous activity in both young and aged PVs. Conclusion: Aging increases PV arrhythmogenesis via abnormal Ca2+ regulation. These findings support the concept that ryanodine receptor dysfunction may result in high PV arrhythmogenesis and aging-related arrhythmogenic vulnerability.

Original languageEnglish
Pages (from-to)1338-1349
Number of pages12
JournalHeart Rhythm
Volume4
Issue number10
DOIs
Publication statusPublished - Oct 2007

Fingerprint

Pulmonary Veins
Calcium
Ryanodine Receptor Calcium Release Channel
Tacrolimus
Sirolimus
Ryanodine
Ouabain
Action Potentials
Calcium-Transporting ATPases
Electrophysiology
Incidence
Sarcoplasmic Reticulum
Microelectrodes
Membrane Potentials
Atrial Fibrillation

Keywords

  • Aging
  • Atrial fibrillation
  • Calcium
  • Pulmonary Veins
  • Ryanodine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Wongcharoen, W., Chen, Y. C., Chen, Y. J., Chen, S. Y., Yeh, H. I., Lin, C. I., & Chen, S. A. (2007). Aging increases pulmonary veins arrhythmogenesis and susceptibility to calcium regulation agents. Heart Rhythm, 4(10), 1338-1349. https://doi.org/10.1016/j.hrthm.2007.06.023

Aging increases pulmonary veins arrhythmogenesis and susceptibility to calcium regulation agents. / Wongcharoen, Wanwarang; Chen, Yao Chang; Chen, Yi Jen; Chen, Szu Ying; Yeh, Huang I.; Lin, Cheng I.; Chen, Shih Ann.

In: Heart Rhythm, Vol. 4, No. 10, 10.2007, p. 1338-1349.

Research output: Contribution to journalArticle

Wongcharoen, Wanwarang ; Chen, Yao Chang ; Chen, Yi Jen ; Chen, Szu Ying ; Yeh, Huang I. ; Lin, Cheng I. ; Chen, Shih Ann. / Aging increases pulmonary veins arrhythmogenesis and susceptibility to calcium regulation agents. In: Heart Rhythm. 2007 ; Vol. 4, No. 10. pp. 1338-1349.
@article{6543886ce624447aae3e50d67812c46d,
title = "Aging increases pulmonary veins arrhythmogenesis and susceptibility to calcium regulation agents",
abstract = "Background: Aging and pulmonary veins (PVs) play a critical role in the pathophysiology of atrial fibrillation. Abnormal Ca2+ regulation and ryanodine receptors are known to contribute to PV arrhythmogenesis. Objective: The purpose of this study was to investigate whether aging alters PV electrophysiology, Ca2+ regulation proteins, and responses to rapamycin, FK-506, ryanodine, and ouabain. Methods: Conventional microelectrodes were used to record action potential and contractility in isolated PV tissue samples in 15 young (age 3 months) and 16 aged (age 3 years) rabbits before and after drug administration. Expression of sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), ryanodine receptor, and Na+/Ca2+ exchanger was evaluated by western blot. Results: Aged PVs had larger amplitude of delayed afterdepolarizations, greater depolarized resting membrane potential, longer action potential duration, and higher incidence of action potential alternans and contractile alternans with increased expression of Na+/Ca2+ exchanger and ryanodine receptor and decreased expression of SERCA2a. Rapamycin (1,10,100 nM), FK-506 (0.01, 0.1, 1 μM), ryanodine (0.1, 1 μM), and ouabain (0.1, 1 μM) concentration-dependently increased PV spontaneous rates and the incidence of delayed afterdepolarizations in young and aged PVs. Compared with results in young PVs, rapamycin and FK-506 in aged PVs increased PV spontaneous rates to a greater extent and exhibited a larger delayed afterdepolarization amplitude. In PVs without spontaneous activity, rapamycin and FK-506 induced spontaneous activity only in aged PVs, but ryanodine and ouabain induced spontaneous activity in both young and aged PVs. Conclusion: Aging increases PV arrhythmogenesis via abnormal Ca2+ regulation. These findings support the concept that ryanodine receptor dysfunction may result in high PV arrhythmogenesis and aging-related arrhythmogenic vulnerability.",
keywords = "Aging, Atrial fibrillation, Calcium, Pulmonary Veins, Ryanodine",
author = "Wanwarang Wongcharoen and Chen, {Yao Chang} and Chen, {Yi Jen} and Chen, {Szu Ying} and Yeh, {Huang I.} and Lin, {Cheng I.} and Chen, {Shih Ann}",
year = "2007",
month = "10",
doi = "10.1016/j.hrthm.2007.06.023",
language = "English",
volume = "4",
pages = "1338--1349",
journal = "Heart Rhythm",
issn = "1547-5271",
publisher = "Elsevier",
number = "10",

}

TY - JOUR

T1 - Aging increases pulmonary veins arrhythmogenesis and susceptibility to calcium regulation agents

AU - Wongcharoen, Wanwarang

AU - Chen, Yao Chang

AU - Chen, Yi Jen

AU - Chen, Szu Ying

AU - Yeh, Huang I.

AU - Lin, Cheng I.

AU - Chen, Shih Ann

PY - 2007/10

Y1 - 2007/10

N2 - Background: Aging and pulmonary veins (PVs) play a critical role in the pathophysiology of atrial fibrillation. Abnormal Ca2+ regulation and ryanodine receptors are known to contribute to PV arrhythmogenesis. Objective: The purpose of this study was to investigate whether aging alters PV electrophysiology, Ca2+ regulation proteins, and responses to rapamycin, FK-506, ryanodine, and ouabain. Methods: Conventional microelectrodes were used to record action potential and contractility in isolated PV tissue samples in 15 young (age 3 months) and 16 aged (age 3 years) rabbits before and after drug administration. Expression of sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), ryanodine receptor, and Na+/Ca2+ exchanger was evaluated by western blot. Results: Aged PVs had larger amplitude of delayed afterdepolarizations, greater depolarized resting membrane potential, longer action potential duration, and higher incidence of action potential alternans and contractile alternans with increased expression of Na+/Ca2+ exchanger and ryanodine receptor and decreased expression of SERCA2a. Rapamycin (1,10,100 nM), FK-506 (0.01, 0.1, 1 μM), ryanodine (0.1, 1 μM), and ouabain (0.1, 1 μM) concentration-dependently increased PV spontaneous rates and the incidence of delayed afterdepolarizations in young and aged PVs. Compared with results in young PVs, rapamycin and FK-506 in aged PVs increased PV spontaneous rates to a greater extent and exhibited a larger delayed afterdepolarization amplitude. In PVs without spontaneous activity, rapamycin and FK-506 induced spontaneous activity only in aged PVs, but ryanodine and ouabain induced spontaneous activity in both young and aged PVs. Conclusion: Aging increases PV arrhythmogenesis via abnormal Ca2+ regulation. These findings support the concept that ryanodine receptor dysfunction may result in high PV arrhythmogenesis and aging-related arrhythmogenic vulnerability.

AB - Background: Aging and pulmonary veins (PVs) play a critical role in the pathophysiology of atrial fibrillation. Abnormal Ca2+ regulation and ryanodine receptors are known to contribute to PV arrhythmogenesis. Objective: The purpose of this study was to investigate whether aging alters PV electrophysiology, Ca2+ regulation proteins, and responses to rapamycin, FK-506, ryanodine, and ouabain. Methods: Conventional microelectrodes were used to record action potential and contractility in isolated PV tissue samples in 15 young (age 3 months) and 16 aged (age 3 years) rabbits before and after drug administration. Expression of sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), ryanodine receptor, and Na+/Ca2+ exchanger was evaluated by western blot. Results: Aged PVs had larger amplitude of delayed afterdepolarizations, greater depolarized resting membrane potential, longer action potential duration, and higher incidence of action potential alternans and contractile alternans with increased expression of Na+/Ca2+ exchanger and ryanodine receptor and decreased expression of SERCA2a. Rapamycin (1,10,100 nM), FK-506 (0.01, 0.1, 1 μM), ryanodine (0.1, 1 μM), and ouabain (0.1, 1 μM) concentration-dependently increased PV spontaneous rates and the incidence of delayed afterdepolarizations in young and aged PVs. Compared with results in young PVs, rapamycin and FK-506 in aged PVs increased PV spontaneous rates to a greater extent and exhibited a larger delayed afterdepolarization amplitude. In PVs without spontaneous activity, rapamycin and FK-506 induced spontaneous activity only in aged PVs, but ryanodine and ouabain induced spontaneous activity in both young and aged PVs. Conclusion: Aging increases PV arrhythmogenesis via abnormal Ca2+ regulation. These findings support the concept that ryanodine receptor dysfunction may result in high PV arrhythmogenesis and aging-related arrhythmogenic vulnerability.

KW - Aging

KW - Atrial fibrillation

KW - Calcium

KW - Pulmonary Veins

KW - Ryanodine

UR - http://www.scopus.com/inward/record.url?scp=34848918916&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34848918916&partnerID=8YFLogxK

U2 - 10.1016/j.hrthm.2007.06.023

DO - 10.1016/j.hrthm.2007.06.023

M3 - Article

VL - 4

SP - 1338

EP - 1349

JO - Heart Rhythm

JF - Heart Rhythm

SN - 1547-5271

IS - 10

ER -