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Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
11:00

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes

Published on: September 18, 2017

Molecular mechanisms of reduced sarcoplasmic reticulum Ca(2+) uptake in human failing left ventricular myocardium

Sudhish Mishra1, Ramesh C Gupta, Nivedita Tiwari

  • 1Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan, USA

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
|March 19, 2002
PubMed

Insights

Heart failure involves reduced sarcoplasmic reticulum Ca(2+) uptake. This study identifies reduced Ca(2+)-ATPase and phospholamban (PLB) phosphorylation as key contributors, suggesting new therapeutic targets for heart failure.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Idiopathic dilated cardiomyopathy leads to heart failure with impaired sarcoplasmic reticulum Ca(2+) uptake.
  • The specific mechanisms underlying this Ca(2+) uptake abnormality remain unclear.

Purpose of the Study:

  • To investigate the molecular mechanisms responsible for decreased sarcoplasmic reticulum Ca(2+) uptake in failing human hearts.
  • To compare protein expression and enzyme activities in failing hearts versus non-failing controls.

Main Methods:

  • Left ventricular tissue from 7 failing hearts (idiopathic dilated cardiomyopathy) and 5 control hearts were analyzed.
  • Levels of sarcoplasmic reticulum proteins (Ca(2+)-ATPase, phospholamban [PLB], calsequestrin) and their phosphorylation states were measured.
  • Activities of Ca(2+)-calmodulin-dependent protein kinase and protein phosphatase were determined, alongside Ca(2+) uptake kinetics.

Main Results:

  • Failing hearts showed reduced maximal velocity and affinity for Ca(2+) uptake.
  • This correlated with decreased Ca(2+)-ATPase, PLB, and serine-16 phosphorylated PLB expression.
  • Protein phosphatase activity was significantly increased in failing hearts.

Conclusions:

  • Impaired Ca(2+) uptake velocity is linked to reduced Ca(2+)-ATPase expression.
  • Reduced affinity is associated with a lower Ca(2+)-ATPase to PLB ratio and decreased serine-16 PLB phosphorylation.
  • Increased protein phosphatase activity may contribute to reduced PLB phosphorylation, suggesting therapeutic potential in targeting phosphatases or enhancing Ca(2+) uptake.
Abstract

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