On the role of junctin in cardiac Ca2+ handling, contractility, and heart failure

Ulrich Gergs, Tobias Berndt, Jan Buskase, Larry R. Jones, Uwe Kirchhefer, Frank U. Müller, Klaus Dieter Schlüter, Wilhelm Schmitz, Joachim Neumann

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Junctin is a transmembrane protein located at the cardiac junctional sarcoplasmic reticulum (SR) and forms a quaternary complex with the Ca 2+ release channel, triadin and calsequestrin. Impaired protein interactions within this complex may alter the Ca2+ sensitivity of the Ca2+ release channel and may lead to cardiac dysfunction, including hypertrophy, depressed contractility, and abnormal Ca2+ transients. To study the expression of junctin and, for comparison, triadin, in heart failure, we measured the levels of these proteins in SR from normal and failing human hearts. Junctin was below our level of detection in SR membranes from failing human hearts, and triadin was downregulated by 22%. To better understand the role of junctin in the regulation of Ca2+ homeostasis and contraction of cardiac myocytes, we used an adenoviral approach to overexpress junctin in isolated rat cardiac myocytes. A recombinant adenovirus encoding the green fluorescent protein served as a control. Infection of myocytes with the junctin-expressing virus resulted in an increased RNA and protein expression of junctin. Ca2+ transients showed a decreased maximum Ca2+ amplitude, and contractility of myocytes was depressed. Our results demonstrate that an increased expression of junctin is associated with an impaired Ca2+ homeostasis. Downregulation of junctin in human heart failure may thus be a compensatory mechanism.

Original languageEnglish (US)
Pages (from-to)H728-H734
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number1
DOIs
StatePublished - Jul 1 2007

Keywords

  • Adenovirus
  • Calcium transient
  • Cardiac myocytes
  • Junctin
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Physiology

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