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Updated: Aug 28, 2026
Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling
Published on: August 1, 2016
Novel cardiac myofilament desensitizing factor released by endocardial and vascular endothelial cells
A M Shah1, A Mebazaa, R C Wetzel
1Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
Insights
Endothelial cells release a novel, stable factor that reduces cardiac myofilament response to calcium, modulating heart contraction and relaxation. This finding reveals a new mechanism in cardiac function regulation.
Area of Science:
- Cardiovascular Physiology
- Endothelial Cell Biology
Background:
- Endocardial and coronary vascular endothelium influence myocardial contraction.
- Mediators and mechanisms of endothelial influence on cardiac function are not well defined.
Purpose of the Study:
- Investigate the effects of endothelial cell superfusate on cardiac myocyte contraction.
- Identify mediators responsible for endothelial-induced changes in myocardial function.
Main Methods:
- Cultured endocardial and vascular endothelial cells were used.
- Superfusate effects on isolated rat cardiac myocyte contraction and intracellular calcium transients were measured.
- Characterization of the active factor (stability, molecular weight, protease resistance) was performed.
Main Results:
- Endothelial cell superfusate induced a potent negative inotropic effect.
- This effect included decreased myocyte twitch amplitude, faster relaxation, and increased diastolic length.
- The activity was stable, low-molecular-weight, protease-resistant, and independent of nitric oxide, prostanoids, cGMP, protein kinase C, or pertussis toxin-sensitive G proteins.
Conclusions:
- Endothelial cells release a novel, stable, low-molecular-weight factor.
- This factor reduces cardiac myofilament sensitivity to calcium, "desensitizing" them.
- This "desensitizing factor" modulates cardiac contraction-relaxation coupling and diastolic tonus.
Background:
Recent studies suggest that both endocardial endothelium and coronary vascular endothelium influence myocardial contraction, but the mediators responsible and their mechanisms of action are not well defined.
Methods And Results:
We investigated the effects of cultured endocardial endothelial and vascular endothelial cell superfusate on contraction and intracellular calcium transients of isolated rat cardiac myocytes. Endothelial cell superfusate induced a potent negative inotropic effect, with a rapid reversible decrease in myocyte twitch amplitude, earlier twitch relaxation, and a significant increase in diastolic length. This effect was not associated with significant changes in intracellular calcium or pH; was not attributable to nitric oxide, prostanoids, cGMP, or protein kinase C activation; and did not involve pertussis toxin-sensitive G proteins. The activity was stable at 37 degrees C for several hours, was not destroyed by protease treatment, and was found in low-molecular-weight (<< 1 kD) superfusate fractions.
Conclusions:
These data suggest the tonic release by endothelial cells of a novel, stable factor that acts predominantly by reducing the response of cardiac myofilaments to calcium (ie, "desensitizes" them). This "desensitizing factor" could rapidly modulate cardiac contraction-relaxation coupling and diastolic tonus and exert distant effects because of its stability.
