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Updated: Jun 23, 2026
07:51
Mechanical Control of Relaxation Using Intact Cardiac Trabeculae
Published on: February 17, 2023
Relaxin alters cardiac myofilament function through a PKC-dependent pathway
Erynn E Shaw1, Philip Wood, Justyna Kulpa
1Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Summary
The pregnancy hormone relaxin (RLX) enhances heart muscle contraction by increasing myofilament force. This effect is mediated by protein kinase C (PKC) signaling, not PKA, altering protein phosphorylation.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Endocrinology
Background:
- The pregnancy hormone relaxin (RLX) is a potent cardiostimulatory peptide.
- Intracellular mechanisms underlying RLX's positive inotropic effects on the heart remain unclear.
- Cardiac myofilament protein phosphorylation influences heart contractility.
Purpose of the Study:
- To investigate if RLX stimulates myofilament activation and alters protein phosphorylation.
- To determine if RLX mediates myocardial effects via Protein Kinase A (PKA) or Protein Kinase C (PKC) activation.
Main Methods:
- Murine myocardium was treated with recombinant H2-RLX, followed by isolation of cardiac myofilaments.
- Analysis of myofilament force development, ATP consumption, and protein phosphorylation levels.
- Immunoblot analysis to assess myofilament-associated PKC isoforms and PKA activity.
Main Results:
- RLX increased cardiac myofilament force development without affecting ATP consumption.
- RLX treatment elevated phosphorylation of myosin binding protein C, troponin T, and troponin I.
- Myofilament-associated PKC-delta increased, while PKC-alpha and -beta(II) decreased; PKA was unaffected.
- PKC inhibition (chelerythrine chloride or rottlerin) blocked RLX-induced changes in myofilament function and phosphorylation.
Conclusions:
- RLX enhances cardiac myofilament force through PKC-delta activation, not PKA.
- RLX-dependent alterations in myofilament protein phosphorylation mediate its cardiostimulatory effects.
- This study elucidates a novel intracellular signaling pathway for relaxin's cardiac actions.
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