Endocardial endothelium modulates myofilament Ca2+ responsiveness in aequorin-loaded ferret myocardium

The influence of selective removal of the endocardial endothelium (by a 1-second exposure to the detergent Triton X-100, 0.5%) on myofilament Ca2+ responsiveness and intracellular Ca2+ transients was studied in ferret papillary muscles loaded with the Ca(2+)-regulated bioluminescent indicator aequorin. The removal of endocardial endothelium produced three major effects: 1) a decrease in peak developed tension and an early onset in isometric relaxation without corresponding changes in the intracellular Ca2+ transient; 2) a rightward shift in the peak [Ca2+]i-peak tension relation with no change in maximum Ca(2+)-activated twitch tension; and 3) a decrease in steady-state tetanic force with a slight increase in the steady-state [Ca2+]i (at 4 mM [Ca2+]o) and an unchanged steady-state tetanic force with a clear increase in the steady-state [Ca2+]i (at 10 mM [Ca2+]o). These results suggest that intact endocardium may enhance performance of the heart by increasing the myofilament Ca2+ responsiveness through endothelium-derived compounds such as endothelin. This hypothesis is supported by our observations that endothelin 1) induced a leftward shift in peak [Ca2+]i-peak tension curve and 2) could reverse the characteristic changes produced by the removal of endocardium.