Role of endothelin-1 receptors in the sarcolemma membrane and the nuclear membrane in the modulation of basal cytosolic and nuclear calcium levels in heart cells

Our previous work in heart cells showed that the nuclear envelope membranes possess receptors, such as those for angiotensin II. Using non-working single cells from the hearts of 10-day chick embryos and the confocal microscopy technique, our present results show that stimulation of endothelin-1 (ET-1) receptors at the sarcolemma membrane induced a dose-dependent sustained increase in basal cytosolic and nuclear calcium levels that was insensitive to the ET_A and ET_B receptor antagonists BQ123 and BQ788. The cytosolic application of ET-1 induced a dose-dependent increase in the sustained basal nuclear Ca²⁺ concentration that was insensitive to BQ123 and BQ788. The ET-1 receptors at the nuclear envelope membrane were more sensitive to ET-1 than those located at the sarcolemma membrane of heart cells. Cytosolic application of ET-1 prevented sustained basal cytosolic Ca²⁺ uptake by the nuclei. The use of an ET-1 fluorescent probe demonstrated the presence of ET-1 receptors at both the sarcolemma membrane and the nuclear envelope membrane. Thus our results suggest that ET-1 receptors that are insensitive to BQ123 and BQ788 are present at both the sarcolemma and nuclear envelope membranes. Extracellular and cytosolic ET-1 may play a role in regulating basal cytosolic and nuclear Ca²⁺ levels in heart cells.