G. Bkaily et al., Presence of functional endothelin-1 receptors in nuclear membranes of human aortic vascular smooth muscle cells, J CARDIO PH, 36, 2000, pp. S414-S417
Citations number
15
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Our previous work showed that the nucleus plays a role in excitation-contra
ction coupling and that the channels and receptors could be present at the
nuclear membrane. In the study reported here, the objective was to test the
hypothesis that endothelin-1 (ET-1) receptors are functional at the level
of the nuclear membranes and that their stimulation importantly regulates f
ree nucleoplasmic Ca2+ level. Using a Flue-3 Ca2+ measurement technique in
human vascular smooth muscle cells (HVSMC), superfusion with increasing con
centrations of extracellular ET-1 induced a dose-dependent sustained increa
se of free cytosolic ([Ca](c)), nuclear ([Ca](n)) Ca2+ and contraction with
an EC50 near 3 x 10(-10) hi. Like the extracellular ET-1, the cytosolic ap
plication of ET-1 using the perforated sarcolemma membrane technique, induc
ed a dose-dependent increase of nuclear free calcium of HVSMC with an EC50
of 2 x 10(-11) M. These results strongly suggest that ET-1 receptors are fu
nctional at the level of the nuclear membranes. Furthermore, the sensitivit
y of ET-1 receptors at the nuclear membrane level seems to be higher than t
hat of the receptors at the sarcolemma membrane. Finally, our results sugge
st that cytosolic ET-1 may play a role in preventing HVSMC nuclear calcium
overload, thus protecting the cells from apoptosis.