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Endothelial inhibition of myofilament calcium response in intact cardiac myocytes
C B Pepper1, D Lang, M J Lewis
1Department of Cardiology, University of Wales College of Medicine, Cardiff, United Kingdom.
Insights
Endothelial cells release factors that impact heart muscle contraction. These factors reduce myofilament calcium response, affecting cardiac performance.
Area of Science:
- Cardiovascular Physiology
- Endothelial Cell Biology
- Cardiac Myocyte Function
Background:
- Endothelial cells are known to influence cardiac function.
- Previous research indicates paracrine factors from endothelial cells can modulate cardiac contractility.
Purpose of the Study:
- To compare the effects of coronary effluent and cultured endothelial cell superfusate on cardiac myocyte contraction.
- To investigate the mechanism by which endothelial factors affect myocyte contractility, specifically the myofilament calcium response.
Main Methods:
- Isolated rat ventricular myocytes loaded with fura 2 were used.
- Comparison of effects from coronary effluent (Langendorff-perfused rat hearts) and cultured vascular endothelial cell superfusate.
- Measurement of isotonic contraction amplitude, myocyte diastolic length, intracellular Ca2+ transient, and myofilament response to Ca2+.
Main Results:
- Both coronary effluent and cultured cell superfusate significantly reduced isotonic contraction amplitude and increased myocyte diastolic length.
- A small decrease in intracellular Ca2+ transient amplitude was observed, insufficient to explain the reduction in twitch.
- Endothelial effluent reduced the steady-state myofilament response to Ca2+ in tetanized myocytes.
Conclusions:
- Endothelial cells, both in situ and in culture, release factors that tonically suppress myofilament calcium responsiveness.
- This suppression of myofilament calcium sensitivity is a key mechanism by which endothelial factors modulate cardiac myocyte contraction.
Abstract:
Recent studies suggest that factors released by endothelial cells can modify contraction of isolated cardiac preparations. We compared the effects of 1) coronary effluent collected from Langendorff-perfused rat hearts and 2) cultured vascular endothelial cell superfusate on isolated fura 2-loaded rat ventricular cardiac myocytes. Coronary and cultured cell effluent produced similar effects. Isotonic contraction amplitude was reduced by 31.6 +/- 2.6 and 70.2 +/- 9.1%, respectively; myocyte diastolic length increased by 0.8 +/- 0.2 and 1.5 +/- 0.4 microns, and time to 50% relaxation fell by 6.2 +/- 1.8 and 10.1 +/- 2.0% (all P < 0.05; n = 29 and 15 myocytes, respectively). A small fall in the amplitude of the intracellular Ca2+ transient was observed (8.5 +/- 1.5 and 10.9 +/- 3.5%, respectively; both P < 0.01), insufficient to account for the reduction in twitch amplitude. In intact myocytes tetanized in the presence of thapsigargin, the steady-state myofilament response to Ca2+ was reduced by coronary and cultured cell effluent. These results suggest that both coronary endothelial cells in situ and cultured endothelial cells tonically release a factor(s) that reduces myofilament Ca2+ response.