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Endothelial cells are required for the cAMP regulation of cardiac contractile proteins
G McClellan1, A Weisberg, L E Lin
1Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia 19104-6085.
Insights
Endothelial cells are crucial for cAMP-dependent regulation of cardiac contractile proteins. Without intact endothelial cells, cyclic AMP (cAMP) cannot increase actomyosin ATPase activity, impacting cardiac muscle function.
Area of Science:
- Cardiovascular Physiology
- Cell Biology
- Biochemistry
Background:
- Cardiac muscle contraction is regulated by cAMP-dependent mechanisms affecting actomyosin ATPase activity.
- Factors from myocardial small arteries and endothelial cells influence cardiac contractile force.
Purpose of the Study:
- To investigate the necessity of endothelial cells for cAMP-mediated regulation of cardiac contractile proteins.
- To elucidate the role of endothelial cells in the cAMP-dependent modulation of actomyosin ATPase activity.
Main Methods:
- Measuring cAMP's effect on actomyosin ATPase activity in rat ventricular trabeculae sections.
- Comparing activity in trabeculae with intact versus damaged (Triton X-100) endocardial endothelial cells.
Main Results:
- cAMP increased actomyosin ATPase activity in trabeculae with intact endothelial cells.
- cAMP failed to alter actomyosin ATPase activity when endothelial cells were damaged.
- Coronary venous effluent's effect on isometric force correlated with cAMP-induced ATPase activity up-regulation.
Conclusions:
- Endothelial cells are essential for the proper functioning of cAMP-dependent regulation of cardiac contractile proteins.
- The myocardium appears to autoregulate by utilizing endothelial-derived factors to modulate cAMP regulation of contractile proteins.
Abstract:
The contractile proteins in mammalian cardiac muscle are regulated by a cAMP-dependent reaction that alters the activity of the actomyosin ATPase. The ATPase activity of cardiac actomyosin has also been shown to depend on factors released by small arteries in the myocardial tissue. Endothelial cells have been implicated in the regulation of the contractile force developed by isolated cardiac tissue. To determine whether endothelial cells are required for the cAMP-dependent regulation of the contractile proteins, the effect of cAMP on the actomyosin ATPase activity was measured in cryostatic sections of isolated, quickly frozen rat ventricular trabeculae. In half of the trabeculae, the endocardial endothelial cells had been damaged by a 1-sec exposure to 0.5% Triton X-100. In trabeculae with intact endothelial cells, cAMP increased actomyosin ATPase activity toward an apparently maximum value. In trabeculae with damaged endothelial cells, cAMP did not change actomyosin ATPase activity. The coronary venous effluent from an isolated heart has already been shown to modify the maximum isometric force developed by an isolated trabecula. The extent to which the force of the isolated trabecula is changed by the coronary venous effluent is closely related to the degree to which cAMP has up-regulated the actomyosin ATPase activity in the isolated heart donating the coronary effluent: the greater the degree of up-regulation of ATPase activity, the greater the increase in force produced by the effluent. These results indicate that endothelial cells are required for the cAMP-dependent regulation of cardiac contractile proteins to function, and these results further suggest that the myocardium autoregulates by modulating the cAMP regulation of contractile proteins with endothelial-derived factors.