Overexpression of junctin causes adaptive changes in cardiac myocyte Ca2+ signaling

Uwe Kirchhefer, Gabriela Hanske, Larry Jones, Isabel Justus, Lars Kaestner, Peter Lipp, Wilhelm Schmitz, Joachim Neumann

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

In cardiac muscle, junctin forms a quaternary protein complex with the ryanodine receptor (RyR), calsequestrin, and triadin 1 at the luminal face of the junctional sarcoplasmic reticulum (jSR). By binding directly the RyR and calsequestrin, junctin may mediate the Ca2+ -dependent regulatory interactions between both proteins. To gain more insight into the underlying mechanisms of impaired contractile relaxation in transgenic mice with cardiac-specific overexpression of junctin (TG), we studied cellular Ca2+ handling in these mice. We found that the SR Ca2+ load was reduced by 22% in cardiomyocytes from TG mice. Consistent with this, the frequency of Ca2+ sparks was diminished by 32%. The decay of spontaneous Ca2+ sparks was prolonged by 117% in TG. This finding was associated with a lower Na+-Ca2+ exchanger (NCX) protein expression (by 67%) and a higher basal RyR phosphorylation at Ser2809 (by 64%) in TG. The shortening- and Δ[Ca]i-frequency relationships (0.5-4 Hz) were flat in TG compared to wild-type (WT) which exhibited a positive staircase for both parameters. Furthermore, increasing stimulation frequencies hastened the time of relaxation and the decay of [Ca]i by a higher percentage in TG. We conclude that the impaired relaxation in TG may result from a reduced NCX expression and/or a higher SR Ca2+ leak. The altered shortening-frequency relationship in TG seems to be a consequence of an impaired excitation-contraction coupling with depressed SR Ca2+ release at higher rates of stimulation. Our data suggest that the more prominent frequency-dependent hastening of relaxation in TG results from a stimulation of SR Ca2+ transport reflected by corresponding changes of [Ca]i.

Original languageEnglish
Pages (from-to)131-142
Number of pages12
JournalCell Calcium
Volume39
Issue number2
DOIs
StatePublished - Feb 2006

Fingerprint

Ryanodine Receptor Calcium Release Channel
Calsequestrin
Cardiac Myocytes
Excitation Contraction Coupling
Proteins
Sarcoplasmic Reticulum
Transgenic Mice
Myocardium
Phosphorylation

Keywords

  • Ca handling
  • Ca release units
  • Ca sparks
  • Cardiac function
  • Excitation-contraction coupling
  • Junctional sarcoplasmic reticulum
  • Transgenic mouse model

ASJC Scopus subject areas

  • Cell Biology
  • Endocrinology

Cite this

Kirchhefer, U., Hanske, G., Jones, L., Justus, I., Kaestner, L., Lipp, P., ... Neumann, J. (2006). Overexpression of junctin causes adaptive changes in cardiac myocyte Ca2+ signaling. Cell Calcium, 39(2), 131-142. https://doi.org/10.1016/j.ceca.2005.10.004

Overexpression of junctin causes adaptive changes in cardiac myocyte Ca2+ signaling. / Kirchhefer, Uwe; Hanske, Gabriela; Jones, Larry; Justus, Isabel; Kaestner, Lars; Lipp, Peter; Schmitz, Wilhelm; Neumann, Joachim.

In: Cell Calcium, Vol. 39, No. 2, 02.2006, p. 131-142.

Research output: Contribution to journalArticle

Kirchhefer, U, Hanske, G, Jones, L, Justus, I, Kaestner, L, Lipp, P, Schmitz, W & Neumann, J 2006, 'Overexpression of junctin causes adaptive changes in cardiac myocyte Ca2+ signaling', Cell Calcium, vol. 39, no. 2, pp. 131-142. https://doi.org/10.1016/j.ceca.2005.10.004
Kirchhefer, Uwe ; Hanske, Gabriela ; Jones, Larry ; Justus, Isabel ; Kaestner, Lars ; Lipp, Peter ; Schmitz, Wilhelm ; Neumann, Joachim. / Overexpression of junctin causes adaptive changes in cardiac myocyte Ca2+ signaling. In: Cell Calcium. 2006 ; Vol. 39, No. 2. pp. 131-142.
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