RGD Reference Report - On the role of junctin in cardiac Ca2+ handling, contractility, and heart failure. - Rat Genome Database

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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.
RGD ID: 7327229
Pubmed: PMID:17400717   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpheart.01187.2006   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dilated cardiomyopathy  IEP 7327229protein:decreased expression:heartRGD 
dilated cardiomyopathy  ISOTRDN (Homo sapiens)7327229; 7327229protein:decreased expression:heartRGD 

Objects Annotated

Genes (Rattus norvegicus)
Trdn  (triadin)

Genes (Mus musculus)
Trdn  (triadin)

Genes (Homo sapiens)
TRDN  (triadin)


Additional Information