title: Nuclear Membranes ETB Receptors Mediate ET-1-induced Increase of Nuclear Calcium in Human Left Ventricular Endocardial Endothelial Cells.
abstract: In fetal human left ventricular endocardial endothelial cells (EECLs), both plasma membrane (PM) ET(A)R and ET(B)R were reported to mediate ET-1-induced increase of intracellular calcium [Ca](i); however, this effect was mediated by ET(A)R in right EECs (EECRs). In this study, we verified whether, as for the PM, nuclear membranes (NMs) ET-1 receptors activation in EECLs and EECRs induce an increase of nuclear calcium ([Ca](n)) and if this effect is mediated through the same receptor type as in PM. Using a plasmalemma-perforated technique and 3D confocal microscopy, our results showed that, as in PM intact cells, superfusion of nuclei of both cell types with cytosolic ET-1 induced a concentration-dependent sustained increase of [Ca](n). In EECRs, the ET(A)R antagonist prevented the effect of ET-1 on [Ca](n) without affecting EECLs. However, in both cell types, the effect of cytosolic ET-1 on [Ca](n) was prevented by the ETBR antagonist. In conclusion, both NMs' ET(A)R and ET(B)R mediated the effect of cytosolic ET-1 on [Ca](n) in EECRs. In contrast, only NMs' ET(B)R activation mediated the effect of cytosolic ET-1 in EECLs. Hence, the type of NMs' receptors mediating the effect of ET-1 on [Ca](n) are different from those of PM mediating the increase in [Ca](i).
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Farah
authors.initials: F
authors.lastname: Jules
authors.forename: Levon
authors.initials: L
authors.lastname: Avedanian
authors.forename: Johny
authors.initials: J
authors.lastname: Al-Khoury
authors.forename: Ramatoulaye
authors.initials: R
authors.lastname: Keita
authors.forename: Alexandre
authors.initials: A
authors.lastname: Normand
authors.forename: Ghassan
authors.initials: G
authors.lastname: Bkaily
authors.forename: Danielle
authors.initials: D
authors.lastname: Jacques
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004699:Endocardium / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology*; D006352:Heart Ventricles; D006801:Humans; D009685:Nuclear Envelope / Q000187:drug effects / Q000502:physiology*; D044023:Receptor, Endothelin B / Q000502:physiology*
chemical_list: C000588596:EDNRB protein, human; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D044023:Receptor, Endothelin B; D002118:Calcium