title: Activation of sarcolemma and nuclear membranes ET-1 receptors regulates transcellular calcium levels in heart and vascular smooth muscle cells.
abstract: The use of an ET-1 fluorescent probe in human heart and vascular smooth muscle cells showed that ET-1 receptors are present at both the sarcolemma and nuclear envelope membranes. The use of immunofluorescence studies showed that the ETA receptor was mainly present at the sarcolemma and cytosolic levels. However, the ETB receptor was present at the sarcolemma and the cytosol, as well as the nuclear envelope membranes and the nucleoplasm. In addition, ET-1 immunoreactivity was seen in the cytosol and the nucleus. Using Ca2+ fluorescent probes such as Fluo-3, Indo 1, and yellow cameleon, as well as confocal microscopy three-dimensional image measurement technique, stimulation of ET-1 receptors at the sarcolemma membranes induced an increase of cytosolic and nuclear free Ca2+ levels. This effect of extracellular ET-1 was blocked by removal of extracellular calcium. Direct stimulation of ET-1 receptors at the nuclear envelope membranes also induced an increase of intranuclear free Ca2+ level. Our results suggest that the stimulation of sarcolemmal Ca2+ influx by ET-1 seems to be due to the activation of ETA and ETB receptors. However, the increase of nucleoplasmic Ca2+ levels by cytosolic ET-1 seems to be mediated via the activation of ETB receptors. Activation of nuclear membranes ETB receptors seems to prevent nuclear Ca2+ overload and may protect the cell from apoptosis.
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada. gbkail01@courrier.usherb.ca
authors.forename: Ghassan
authors.initials: G
authors.lastname: Bkaily
authors.forename: Sanaa
authors.initials: S
authors.lastname: Choufani
authors.forename: Sawsan
authors.initials: S
authors.lastname: Sader
authors.forename: Danielle
authors.initials: D
authors.lastname: Jacques
authors.forename: Pedro
authors.initials: P
authors.lastname: d'Orléans-Juste
authors.forename: Moni
authors.initials: M
authors.lastname: Nader
authors.forename: Ghada
authors.initials: G
authors.lastname: Kurban
authors.forename: Maud
authors.initials: M
authors.lastname: Kamal
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism*; D017466:Receptors, Endothelin / Q000819:agonists / Q000378:metabolism*; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D017466:Receptors, Endothelin; D002118:Calcium