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Updated: Jun 25, 2026
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Analysis of Cardiac Contractile Dysfunction and Ca2+ Transients in Rodent Myocytes
Published on: May 25, 2022
Protein phosphatase 2A contributes to the cardiac dysfunction induced by endotoxemia
Melanie Marshall1, Narayana Anilkumar, Joanne Layland
1Cardiovascular Division, Department of Cardiology, King's College London, James Black Centre, London SE5 9NU, UK. melanie.marshall@kcl.ac.uk
Cardiovascular Research
|February 10, 2009
Summary
Sepsis impairs heart function by increasing cardiac troponin I (cTnI) phosphorylation. Modulating protein phosphatase 2A (PP2A) activity can reverse this sepsis-induced cardiac dysfunction.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Sepsis-associated cardiac dysfunction involves impaired cardiomyocyte function.
- This dysfunction is partly due to decreased myofilament Ca(2+) sensitivity caused by increased cardiac troponin I (cTnI) phosphorylation at Ser23/24.
- Protein phosphatase 2A (PP2A) activity regulates cTnI dephosphorylation, and its modulation can counteract beta-adrenergic stimulation via muscarinic and adenosine A(1)-receptor agonists.
Purpose of the Study:
- To investigate whether modulating PP2A activity and subsequent cTnI phosphorylation can ameliorate sepsis-induced contractile dysfunction.
Main Methods:
- Cardiomyocytes and heart homogenates were isolated from control and lipopolysaccharide (LPS)-injected mice.
- Cardiac troponin I (cTnI) phosphorylation, cardiomyocyte contraction, Ca(2+)-transients, and protein phosphatase 2A (PP2A) activity and expression were assessed.
- Pharmacological agents including adenosine A(1) agonist cyclopentyladenosine (CPA) and protein kinase A inhibitor H89 were used.
Main Results:
- LPS injection increased cTnI phosphorylation and reduced cardiomyocyte contraction amplitude without altering Ca(2+)-transients.
- Treatment with CPA or H89 attenuated LPS-induced contractile dysfunction; co-treatment completely reversed it.
- Septic hearts showed reduced PP2A expression and activity, which was restored by CPA treatment, alongside changes in PP2A methylation status.
Conclusions:
- Sustained cTnI phosphorylation is a key factor in sepsis-induced cardiac contractile dysfunction.
- Modulating PP2A activity offers a potential therapeutic strategy to improve cardiac function during sepsis.
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