Intracellular calcium changes and tachycardia-induced contractile dysfunction in canine atrial myocytes

Hui Sun, Denis Chartier, Normand Leblanc, Stanley Nattel

Research output: Contribution to journalArticle

Abstract

Objectives: Indirect evidence suggests a role for Ca2+-overload in electrical and mechanical alterations caused by atrial tachycardia. The present study assessed the alterations in cellular [Ca2+] and contractile function caused by rapid atrial cellular activation. Methods: Intracellular Ca2+ transients (CaT) and cell shortening (CS) were measured by microfluorometry (Indo-1 AM) and video edge-detection in isolated, field-stimulated canine atrial myocytes (37°C). Results: Abrupt increases in frequency (0.3-3 Hz) caused rapid increases in diastolic [Ca2+]i (DCa) that were maintained during rapid-pacing for up to 50 min. When short-term (3-min) rapid-pacing was imposed, CaT and CS increased initially upon returning to 0.3 Hz, but then declined rapidly to 64±5 and 49±7%, respectively, of pre-tachycardia values, returning to control after ∼15 min. Post-tachycardia CaT and CS reductions were prevented by decreasing [Ca2+]o during tachycardia to prevent Ca2+-overload. CS reductions correlated with indices of Ca2+ loading during tachycardia. Restoration of CaT to normal during post-tachycardia contractile dysfunction (by increasing [Ca2+]o) returned CS to normal, indicating that reduced Ca2+ release, not reduced myofilament Ca2+-sensitivity, caused post-tachycardia contractile failure. Estimation of sarcoplasmic-reticulum Ca2+-stores (caffeine-induced Ca2+-release) confirmed tachycardia-induced Ca2+-loading and suggested that reduced Ca2+-stores decreased Ca2+-release post-tachycardia. Conclusions: Atrial tachycardia increases cellular Ca2+-loading, leading to post-tachycardia abnormalities in Ca2+-handling that produce contractile dysfunction. These findings are the first direct evidence for the frequently-postulated role of Ca2+-overload in tachycardia-induced abnormalities of atrial function.

Original languageEnglish (US)
Pages (from-to)751-761
Number of pages11
JournalCardiovascular Research
Volume49
Issue number4
DOIs
StatePublished - 2001
Externally publishedYes

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Tachycardia
Muscle Cells
Canidae
Calcium
Atrial Function
Cytophotometry
Myofibrils
Sarcoplasmic Reticulum
Caffeine

Keywords

  • Arrhythmia (mechanisms)
  • Atrial function
  • Calcium (cellular)
  • e-c coupling
  • Remodelling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Intracellular calcium changes and tachycardia-induced contractile dysfunction in canine atrial myocytes. / Sun, Hui; Chartier, Denis; Leblanc, Normand; Nattel, Stanley.

In: Cardiovascular Research, Vol. 49, No. 4, 2001, p. 751-761.

Research output: Contribution to journalArticle

Sun, Hui ; Chartier, Denis ; Leblanc, Normand ; Nattel, Stanley. / Intracellular calcium changes and tachycardia-induced contractile dysfunction in canine atrial myocytes. In: Cardiovascular Research. 2001 ; Vol. 49, No. 4. pp. 751-761.
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abstract = "Objectives: Indirect evidence suggests a role for Ca2+-overload in electrical and mechanical alterations caused by atrial tachycardia. The present study assessed the alterations in cellular [Ca2+] and contractile function caused by rapid atrial cellular activation. Methods: Intracellular Ca2+ transients (CaT) and cell shortening (CS) were measured by microfluorometry (Indo-1 AM) and video edge-detection in isolated, field-stimulated canine atrial myocytes (37°C). Results: Abrupt increases in frequency (0.3-3 Hz) caused rapid increases in diastolic [Ca2+]i (DCa) that were maintained during rapid-pacing for up to 50 min. When short-term (3-min) rapid-pacing was imposed, CaT and CS increased initially upon returning to 0.3 Hz, but then declined rapidly to 64±5 and 49±7{\%}, respectively, of pre-tachycardia values, returning to control after ∼15 min. Post-tachycardia CaT and CS reductions were prevented by decreasing [Ca2+]o during tachycardia to prevent Ca2+-overload. CS reductions correlated with indices of Ca2+ loading during tachycardia. Restoration of CaT to normal during post-tachycardia contractile dysfunction (by increasing [Ca2+]o) returned CS to normal, indicating that reduced Ca2+ release, not reduced myofilament Ca2+-sensitivity, caused post-tachycardia contractile failure. Estimation of sarcoplasmic-reticulum Ca2+-stores (caffeine-induced Ca2+-release) confirmed tachycardia-induced Ca2+-loading and suggested that reduced Ca2+-stores decreased Ca2+-release post-tachycardia. Conclusions: Atrial tachycardia increases cellular Ca2+-loading, leading to post-tachycardia abnormalities in Ca2+-handling that produce contractile dysfunction. These findings are the first direct evidence for the frequently-postulated role of Ca2+-overload in tachycardia-induced abnormalities of atrial function.",
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AU - Chartier, Denis

AU - Leblanc, Normand

AU - Nattel, Stanley

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N2 - Objectives: Indirect evidence suggests a role for Ca2+-overload in electrical and mechanical alterations caused by atrial tachycardia. The present study assessed the alterations in cellular [Ca2+] and contractile function caused by rapid atrial cellular activation. Methods: Intracellular Ca2+ transients (CaT) and cell shortening (CS) were measured by microfluorometry (Indo-1 AM) and video edge-detection in isolated, field-stimulated canine atrial myocytes (37°C). Results: Abrupt increases in frequency (0.3-3 Hz) caused rapid increases in diastolic [Ca2+]i (DCa) that were maintained during rapid-pacing for up to 50 min. When short-term (3-min) rapid-pacing was imposed, CaT and CS increased initially upon returning to 0.3 Hz, but then declined rapidly to 64±5 and 49±7%, respectively, of pre-tachycardia values, returning to control after ∼15 min. Post-tachycardia CaT and CS reductions were prevented by decreasing [Ca2+]o during tachycardia to prevent Ca2+-overload. CS reductions correlated with indices of Ca2+ loading during tachycardia. Restoration of CaT to normal during post-tachycardia contractile dysfunction (by increasing [Ca2+]o) returned CS to normal, indicating that reduced Ca2+ release, not reduced myofilament Ca2+-sensitivity, caused post-tachycardia contractile failure. Estimation of sarcoplasmic-reticulum Ca2+-stores (caffeine-induced Ca2+-release) confirmed tachycardia-induced Ca2+-loading and suggested that reduced Ca2+-stores decreased Ca2+-release post-tachycardia. Conclusions: Atrial tachycardia increases cellular Ca2+-loading, leading to post-tachycardia abnormalities in Ca2+-handling that produce contractile dysfunction. These findings are the first direct evidence for the frequently-postulated role of Ca2+-overload in tachycardia-induced abnormalities of atrial function.

AB - Objectives: Indirect evidence suggests a role for Ca2+-overload in electrical and mechanical alterations caused by atrial tachycardia. The present study assessed the alterations in cellular [Ca2+] and contractile function caused by rapid atrial cellular activation. Methods: Intracellular Ca2+ transients (CaT) and cell shortening (CS) were measured by microfluorometry (Indo-1 AM) and video edge-detection in isolated, field-stimulated canine atrial myocytes (37°C). Results: Abrupt increases in frequency (0.3-3 Hz) caused rapid increases in diastolic [Ca2+]i (DCa) that were maintained during rapid-pacing for up to 50 min. When short-term (3-min) rapid-pacing was imposed, CaT and CS increased initially upon returning to 0.3 Hz, but then declined rapidly to 64±5 and 49±7%, respectively, of pre-tachycardia values, returning to control after ∼15 min. Post-tachycardia CaT and CS reductions were prevented by decreasing [Ca2+]o during tachycardia to prevent Ca2+-overload. CS reductions correlated with indices of Ca2+ loading during tachycardia. Restoration of CaT to normal during post-tachycardia contractile dysfunction (by increasing [Ca2+]o) returned CS to normal, indicating that reduced Ca2+ release, not reduced myofilament Ca2+-sensitivity, caused post-tachycardia contractile failure. Estimation of sarcoplasmic-reticulum Ca2+-stores (caffeine-induced Ca2+-release) confirmed tachycardia-induced Ca2+-loading and suggested that reduced Ca2+-stores decreased Ca2+-release post-tachycardia. Conclusions: Atrial tachycardia increases cellular Ca2+-loading, leading to post-tachycardia abnormalities in Ca2+-handling that produce contractile dysfunction. These findings are the first direct evidence for the frequently-postulated role of Ca2+-overload in tachycardia-induced abnormalities of atrial function.

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