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

Authors: Gergs, U  Berndt, T  Buskase, J  Jones, LR  Kirchhefer, U  Muller, FU  Schluter, KD  Schmitz, W  Neumann, J 
Citation: Gergs U, etal., Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H728-34. Epub 2007 Mar 30.
Pubmed: (View Article at PubMed) PMID:17400717
DOI: Full-text: DOI:10.1152/ajpheart.01187.2006

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 Ca(2+) sensitivity of the Ca(2+) release channel and may lead to cardiac dysfunction, including hypertrophy, depressed contractility, and abnormal Ca(2+) 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 Ca(2+) 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. Ca(2+) transients showed a decreased maximum Ca(2+) amplitude, and contractility of myocytes was depressed. Our results demonstrate that an increased expression of junctin is associated with an impaired Ca(2+) homeostasis. Downregulation of junctin in human heart failure may thus be a compensatory mechanism.

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CRRD Object Information
CRRD ID: 7327229
Created: 2013-09-17
Species: All species
Last Modified: 2013-09-17
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.