Age-dependent biochemical and contractile properties in atrium of transgenic mice overexpressing junctin

Uwe Kirchhefer, Hideo A. Baba, Gabriela Hanske, Larry Jones, Paulus Kirchhof, Wilhelm Schmitz, Joachim Neumann

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Junctin is a transmembrane protein of the cardiac junctional sarcoplasmic reticulum (SR) that binds to the ryanodine receptor, calsequestrin, and triadin 1. This quaternary protein complex is thought to facilitate SR Ca2+ release. To improve our understanding of the contribution of junctin to the regulation of SR function, we examined the age-dependent effects of junctin overexpression in the atrium of 3-, 6-, and 18-wk-old transgenic mice. The ratio of atrial weight and body weight was unchanged between junctin-overexpressing (JCN) and wild-type (WT) mice at all ages investigated (n = 6-8). The protein expression of triadin 1 was decreased starting in 3-wk-old JCN atria (by 69%), whereas the expression of the ryanodine receptor was diminished in 6- (by 48%) and 18-wk-old (by 57%) JCN atria compared with age-matched WT atria. Force of contraction was decreased by 35% in 18-wk-old JCN compared with age-matched WT left atrial muscle strips, which was accompanied by a prolonged time of relaxation (48.1 ± 0.9 vs. 44.2 ± 0.8 ms, respectively, n = 6-8, P < 0.05). The spontaneous beating rate of isolated right atria was higher in 18-wk-old JCN mice compared with age-matched WT mice (389 ± 10 vs. 357 ± 6 beats/min, respectively, n = 6-8, P < 0.05). Heart rate was lower by 9% in telemetric ECG recordings in 18-wk-old JCN mice during stress tests. Three-week-old JCN atria exhibited a higher potentiation of force of contraction at rest pauses of 30 s (by 13%) and of 300 s (by 35%), suggesting increased SR Ca2+ content. This was consistent with the higher force of contraction in 3-wk-old JCN atria (by 29%) compared with age-matched WT atria (by 10%) under the administration of caffeine. We conclude that in 3-wk-old atria, junctin overexpression was associated with a reduced expression of triadin 1 resulting in a higher SR Ca2+ load without changes in contractility or heart rate. In 6-wk-old JCN atria, the compensatory downregulation of the ryanodine receptor may offset the effects of junctin overexpression. Finally, the progressive decrease in ryanodine receptor density may contribute to the decreased atrial contractility and lower heart rate during stress in 18-wk-old JCN mice.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number5 56-5
DOIs
StatePublished - Nov 2004

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Sarcoplasmic Reticulum
Ryanodine Receptor Calcium Release Channel
Transgenic Mice
Heart Rate
Calsequestrin
Proteins
Caffeine
Heart Atria
Exercise Test
Electrocardiography
Down-Regulation
Body Weight
Weights and Measures
Muscles
triadin

Keywords

  • Calcium handling
  • Force of contraction
  • Heart rate
  • Protein expression
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Physiology

Cite this

Age-dependent biochemical and contractile properties in atrium of transgenic mice overexpressing junctin. / Kirchhefer, Uwe; Baba, Hideo A.; Hanske, Gabriela; Jones, Larry; Kirchhof, Paulus; Schmitz, Wilhelm; Neumann, Joachim.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 287, No. 5 56-5, 11.2004.

Research output: Contribution to journalArticle

Kirchhefer, Uwe ; Baba, Hideo A. ; Hanske, Gabriela ; Jones, Larry ; Kirchhof, Paulus ; Schmitz, Wilhelm ; Neumann, Joachim. / Age-dependent biochemical and contractile properties in atrium of transgenic mice overexpressing junctin. In: American Journal of Physiology - Heart and Circulatory Physiology. 2004 ; Vol. 287, No. 5 56-5.
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abstract = "Junctin is a transmembrane protein of the cardiac junctional sarcoplasmic reticulum (SR) that binds to the ryanodine receptor, calsequestrin, and triadin 1. This quaternary protein complex is thought to facilitate SR Ca2+ release. To improve our understanding of the contribution of junctin to the regulation of SR function, we examined the age-dependent effects of junctin overexpression in the atrium of 3-, 6-, and 18-wk-old transgenic mice. The ratio of atrial weight and body weight was unchanged between junctin-overexpressing (JCN) and wild-type (WT) mice at all ages investigated (n = 6-8). The protein expression of triadin 1 was decreased starting in 3-wk-old JCN atria (by 69{\%}), whereas the expression of the ryanodine receptor was diminished in 6- (by 48{\%}) and 18-wk-old (by 57{\%}) JCN atria compared with age-matched WT atria. Force of contraction was decreased by 35{\%} in 18-wk-old JCN compared with age-matched WT left atrial muscle strips, which was accompanied by a prolonged time of relaxation (48.1 ± 0.9 vs. 44.2 ± 0.8 ms, respectively, n = 6-8, P < 0.05). The spontaneous beating rate of isolated right atria was higher in 18-wk-old JCN mice compared with age-matched WT mice (389 ± 10 vs. 357 ± 6 beats/min, respectively, n = 6-8, P < 0.05). Heart rate was lower by 9{\%} in telemetric ECG recordings in 18-wk-old JCN mice during stress tests. Three-week-old JCN atria exhibited a higher potentiation of force of contraction at rest pauses of 30 s (by 13{\%}) and of 300 s (by 35{\%}), suggesting increased SR Ca2+ content. This was consistent with the higher force of contraction in 3-wk-old JCN atria (by 29{\%}) compared with age-matched WT atria (by 10{\%}) under the administration of caffeine. We conclude that in 3-wk-old atria, junctin overexpression was associated with a reduced expression of triadin 1 resulting in a higher SR Ca2+ load without changes in contractility or heart rate. In 6-wk-old JCN atria, the compensatory downregulation of the ryanodine receptor may offset the effects of junctin overexpression. Finally, the progressive decrease in ryanodine receptor density may contribute to the decreased atrial contractility and lower heart rate during stress in 18-wk-old JCN mice.",
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AU - Schmitz, Wilhelm

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N2 - Junctin is a transmembrane protein of the cardiac junctional sarcoplasmic reticulum (SR) that binds to the ryanodine receptor, calsequestrin, and triadin 1. This quaternary protein complex is thought to facilitate SR Ca2+ release. To improve our understanding of the contribution of junctin to the regulation of SR function, we examined the age-dependent effects of junctin overexpression in the atrium of 3-, 6-, and 18-wk-old transgenic mice. The ratio of atrial weight and body weight was unchanged between junctin-overexpressing (JCN) and wild-type (WT) mice at all ages investigated (n = 6-8). The protein expression of triadin 1 was decreased starting in 3-wk-old JCN atria (by 69%), whereas the expression of the ryanodine receptor was diminished in 6- (by 48%) and 18-wk-old (by 57%) JCN atria compared with age-matched WT atria. Force of contraction was decreased by 35% in 18-wk-old JCN compared with age-matched WT left atrial muscle strips, which was accompanied by a prolonged time of relaxation (48.1 ± 0.9 vs. 44.2 ± 0.8 ms, respectively, n = 6-8, P < 0.05). The spontaneous beating rate of isolated right atria was higher in 18-wk-old JCN mice compared with age-matched WT mice (389 ± 10 vs. 357 ± 6 beats/min, respectively, n = 6-8, P < 0.05). Heart rate was lower by 9% in telemetric ECG recordings in 18-wk-old JCN mice during stress tests. Three-week-old JCN atria exhibited a higher potentiation of force of contraction at rest pauses of 30 s (by 13%) and of 300 s (by 35%), suggesting increased SR Ca2+ content. This was consistent with the higher force of contraction in 3-wk-old JCN atria (by 29%) compared with age-matched WT atria (by 10%) under the administration of caffeine. We conclude that in 3-wk-old atria, junctin overexpression was associated with a reduced expression of triadin 1 resulting in a higher SR Ca2+ load without changes in contractility or heart rate. In 6-wk-old JCN atria, the compensatory downregulation of the ryanodine receptor may offset the effects of junctin overexpression. Finally, the progressive decrease in ryanodine receptor density may contribute to the decreased atrial contractility and lower heart rate during stress in 18-wk-old JCN mice.

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KW - Force of contraction

KW - Heart rate

KW - Protein expression

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