Influence of a constitutive increase in myofilament Ca2+- sensitivity on Ca2+-fluxes and contraction of mouse heart ventricular myocytes

Jose L. Puglisi, Paul H. Goldspink, Aldrin V Gomes, Megan S. Utter, Donald M Bers, R. John Solaro

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Chronic increases in myofilament Ca2+-sensitivity in the heart are known to alter gene expression potentially modifying Ca2+- homeostasis and inducing arrhythmias. We tested age-dependent effects of a chronic increase in myofilament Ca2+-sensitivity on induction of altered alter gene expression and activity of Ca2+ transport systems in cardiac myocytes. Our approach was to determine the relative contributions of the major mechanisms responsible for restoring Ca2+ to basal levels in field stimulated ventricular myocytes. Comparisons were made from ventricular myocytes isolated from non-transgenic (NTG) controls and transgenic mice expressing the fetal, slow skeletal troponin I (TG-ssTnI) in place of cardiac TnI (cTnI). Replacement of cTnI by ssTnI induces an increase in myofilament Ca2+-sensitivity. Comparisons included myocytes from relatively young (5-7 months) and older mice (11-13 months). Employing application of caffeine in normal Tyrode and in 0Na+ 0Ca2+ solution, we were able to dissect the contribution of the sarcoplasmic reticulum Ca2+ pump (SR Ca2+-ATPase), the Na+/Ca2+ exchanger (NCX), and "slow mechanisms" representing the activity of the sarcolemmal Ca2+ pump and the mitochondrial Ca2+ uniporter. The relative contribution of the SR Ca2+-ATPase to restoration of basal Ca2+ levels in younger TG-ssTnI myocytes was lower than in NTG (81.12 ± 2.8% vs 92.70 ± 1.02%), but the same in the older myocytes. Younger and older NTG myocytes demonstrated similar contributions from the SR Ca2+-ATPase and NCX to restoration of basal Ca2+. However, the slow mechanisms for Ca2+ removal were increased in the older NTG (3.4 ± 0.3%) vs the younger NTG myocytes (1.4 ± 0.1%). Compared to NTG, younger TG-ssTnI myocytes demonstrated a significantly bigger contribution of the NCX (16 ± 2.7% in TG vs 6.9 ± 0.9% in NTG) and slow mechanisms (3.3 ± 0.4% in TG vs 1.4 ± 0.1% in NTG). In older TG-ssTnI myocytes the contributions were not significantly different from NTG (NCX: 4.9 ± 0.6% in TG vs 5.5 ± 0.7% in NTG; slow mechanisms: 2.5 ± 0.3% in TG vs 3.4 ± 0.3% in NTG). Our data indicate that constitutive increases in myofilament Ca2+-sensitivity alter the relative significance of the NCX transport system involved in Ca 2+-homeostasis only in a younger group of mice. This modification may be of significance in early changes in altered gene expression and electrical stability hearts with increased myofilament Ca-sensitivity.

Original languageEnglish (US)
Pages (from-to)50-59
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume552-553
DOIs
StatePublished - Jul 15 2014

Fingerprint

Calcium-Transporting ATPases
Myofibrils
Gene expression
Muscle Cells
Fluxes
Restoration
Pumps
Troponin I
Caffeine
Gene Expression
Homeostasis
Sarcoplasmic Reticulum
Cardiac Myocytes
Transgenic Mice
Cardiac Arrhythmias

Keywords

  • Arrhythmia
  • Ca-sensitizer
  • Hypertrophic cardiomyopathy
  • Troponin I

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Influence of a constitutive increase in myofilament Ca2+- sensitivity on Ca2+-fluxes and contraction of mouse heart ventricular myocytes. / Puglisi, Jose L.; Goldspink, Paul H.; Gomes, Aldrin V; Utter, Megan S.; Bers, Donald M; Solaro, R. John.

In: Archives of Biochemistry and Biophysics, Vol. 552-553, 15.07.2014, p. 50-59.

Research output: Contribution to journalArticle

Puglisi, Jose L. ; Goldspink, Paul H. ; Gomes, Aldrin V ; Utter, Megan S. ; Bers, Donald M ; Solaro, R. John. / Influence of a constitutive increase in myofilament Ca2+- sensitivity on Ca2+-fluxes and contraction of mouse heart ventricular myocytes. In: Archives of Biochemistry and Biophysics. 2014 ; Vol. 552-553. pp. 50-59.
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T1 - Influence of a constitutive increase in myofilament Ca2+- sensitivity on Ca2+-fluxes and contraction of mouse heart ventricular myocytes

AU - Puglisi, Jose L.

AU - Goldspink, Paul H.

AU - Gomes, Aldrin V

AU - Utter, Megan S.

AU - Bers, Donald M

AU - Solaro, R. John

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N2 - Chronic increases in myofilament Ca2+-sensitivity in the heart are known to alter gene expression potentially modifying Ca2+- homeostasis and inducing arrhythmias. We tested age-dependent effects of a chronic increase in myofilament Ca2+-sensitivity on induction of altered alter gene expression and activity of Ca2+ transport systems in cardiac myocytes. Our approach was to determine the relative contributions of the major mechanisms responsible for restoring Ca2+ to basal levels in field stimulated ventricular myocytes. Comparisons were made from ventricular myocytes isolated from non-transgenic (NTG) controls and transgenic mice expressing the fetal, slow skeletal troponin I (TG-ssTnI) in place of cardiac TnI (cTnI). Replacement of cTnI by ssTnI induces an increase in myofilament Ca2+-sensitivity. Comparisons included myocytes from relatively young (5-7 months) and older mice (11-13 months). Employing application of caffeine in normal Tyrode and in 0Na+ 0Ca2+ solution, we were able to dissect the contribution of the sarcoplasmic reticulum Ca2+ pump (SR Ca2+-ATPase), the Na+/Ca2+ exchanger (NCX), and "slow mechanisms" representing the activity of the sarcolemmal Ca2+ pump and the mitochondrial Ca2+ uniporter. The relative contribution of the SR Ca2+-ATPase to restoration of basal Ca2+ levels in younger TG-ssTnI myocytes was lower than in NTG (81.12 ± 2.8% vs 92.70 ± 1.02%), but the same in the older myocytes. Younger and older NTG myocytes demonstrated similar contributions from the SR Ca2+-ATPase and NCX to restoration of basal Ca2+. However, the slow mechanisms for Ca2+ removal were increased in the older NTG (3.4 ± 0.3%) vs the younger NTG myocytes (1.4 ± 0.1%). Compared to NTG, younger TG-ssTnI myocytes demonstrated a significantly bigger contribution of the NCX (16 ± 2.7% in TG vs 6.9 ± 0.9% in NTG) and slow mechanisms (3.3 ± 0.4% in TG vs 1.4 ± 0.1% in NTG). In older TG-ssTnI myocytes the contributions were not significantly different from NTG (NCX: 4.9 ± 0.6% in TG vs 5.5 ± 0.7% in NTG; slow mechanisms: 2.5 ± 0.3% in TG vs 3.4 ± 0.3% in NTG). Our data indicate that constitutive increases in myofilament Ca2+-sensitivity alter the relative significance of the NCX transport system involved in Ca 2+-homeostasis only in a younger group of mice. This modification may be of significance in early changes in altered gene expression and electrical stability hearts with increased myofilament Ca-sensitivity.

AB - Chronic increases in myofilament Ca2+-sensitivity in the heart are known to alter gene expression potentially modifying Ca2+- homeostasis and inducing arrhythmias. We tested age-dependent effects of a chronic increase in myofilament Ca2+-sensitivity on induction of altered alter gene expression and activity of Ca2+ transport systems in cardiac myocytes. Our approach was to determine the relative contributions of the major mechanisms responsible for restoring Ca2+ to basal levels in field stimulated ventricular myocytes. Comparisons were made from ventricular myocytes isolated from non-transgenic (NTG) controls and transgenic mice expressing the fetal, slow skeletal troponin I (TG-ssTnI) in place of cardiac TnI (cTnI). Replacement of cTnI by ssTnI induces an increase in myofilament Ca2+-sensitivity. Comparisons included myocytes from relatively young (5-7 months) and older mice (11-13 months). Employing application of caffeine in normal Tyrode and in 0Na+ 0Ca2+ solution, we were able to dissect the contribution of the sarcoplasmic reticulum Ca2+ pump (SR Ca2+-ATPase), the Na+/Ca2+ exchanger (NCX), and "slow mechanisms" representing the activity of the sarcolemmal Ca2+ pump and the mitochondrial Ca2+ uniporter. The relative contribution of the SR Ca2+-ATPase to restoration of basal Ca2+ levels in younger TG-ssTnI myocytes was lower than in NTG (81.12 ± 2.8% vs 92.70 ± 1.02%), but the same in the older myocytes. Younger and older NTG myocytes demonstrated similar contributions from the SR Ca2+-ATPase and NCX to restoration of basal Ca2+. However, the slow mechanisms for Ca2+ removal were increased in the older NTG (3.4 ± 0.3%) vs the younger NTG myocytes (1.4 ± 0.1%). Compared to NTG, younger TG-ssTnI myocytes demonstrated a significantly bigger contribution of the NCX (16 ± 2.7% in TG vs 6.9 ± 0.9% in NTG) and slow mechanisms (3.3 ± 0.4% in TG vs 1.4 ± 0.1% in NTG). In older TG-ssTnI myocytes the contributions were not significantly different from NTG (NCX: 4.9 ± 0.6% in TG vs 5.5 ± 0.7% in NTG; slow mechanisms: 2.5 ± 0.3% in TG vs 3.4 ± 0.3% in NTG). Our data indicate that constitutive increases in myofilament Ca2+-sensitivity alter the relative significance of the NCX transport system involved in Ca 2+-homeostasis only in a younger group of mice. This modification may be of significance in early changes in altered gene expression and electrical stability hearts with increased myofilament Ca-sensitivity.

KW - Arrhythmia

KW - Ca-sensitizer

KW - Hypertrophic cardiomyopathy

KW - Troponin I

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