Receptors and Channels of Nuclear Envelope Membranes as a New Target for Drug Action

  • Ghassan Bkaily
  • Danielle Jacques
  • Pedro D’orléans Juste
Chapter
Part of the Progress in Experimental Cardiology book series (PREC, volume 10)

Summary

The use of confocal microscopy and fluorescent dyes permitted us to show that the nucleus plays an important role in excitation-contraction and secretion coupling of several excitable and non excitable cells. In addition, our group suggested that, like the sarcolemmal membrane, the nuclear envelope membrane possesses receptor s and channels which may play an important role in modulating Ca2+ influx and cytosolic Ca2+ buffering capacity of the nucleus.

Our results showed that the nucleus plays a role as a cytosolic Ca2+ buffer during spontaneous contraction of heart cells as well as during stimulation of cell surface membrane receptors of vascular endothelial and smooth muscle cells.

Using isolated nuclei of cardiomyocytes, vascular endothelial and smooth muscle cells, our results showed that receptors and channels are present at the nuclear envelope membranes. Our results also showed that receptors, such as Ang II and ET-1 receptors, undergo internalization and nuclear translocation and that the nucleus could be implicated in protein synthesis of these receptors. These results demonstrate that like the sarcolemmal membrane, the nuclear envelope membranes possesses channels and G-protein-coupled receptors that could be a new target for drug action.

Key words

Nucleus Ca2+ R-type Ca2+ channel receptors heart vascular endothelial cells smooth muscle cells Ang II ET-1 bradykinin 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bkaily G. 1994. The possible role of Ca2+ and K+ channels in VSM pathophysiology. In: Ionic Channels in Vascular Smooth Muscle. Ed G. Bkaily 103–113. Austin, TX: Molecular Biology Intelligence Unit, R.G. Landes.Google Scholar
  2. 2.
    Means AR. 1994. Calcium, calmodulin and cell regulation. FEBS Lett 347:1–4.PubMedCrossRefGoogle Scholar
  3. 3.
    Peunova N, Enikolopov G. 1993. Amplicifaction of calcium-induced gene transcription by nitricoxide in neuronal cells. Nature 364:450–453.PubMedCrossRefGoogle Scholar
  4. 4.
    Hardingham GE, Chawala S, Johnson CM, Bading H. 1997. Distinct function of nuclear and cytoplasmic calcium in the control of gene expression. Nature 385:260–265.PubMedCrossRefGoogle Scholar
  5. 5.
    Czubryt MP, Ramjiawan B, Gilchrist JSC, Massaeli H, Pierce GN. 1996. The presence and partitioning of calcium binding proteins in hepatic and cardiac nuclei. J Mol Cell Cardiol 28:455–465.PubMedCrossRefGoogle Scholar
  6. 6.
    Steinhardt RA, Alderton J. 1998. Intracellular free calcium rise triggers nuclear envelope breakdown in the sea urchin embryo. Nature 332:364–366.CrossRefGoogle Scholar
  7. 7.
    Nicotera P, Rossi AD. 1994. Nuclear Ca2+: Physiological regulation and role in apoptosis. Mol Cell Biochem 135:89–98.PubMedCrossRefGoogle Scholar
  8. 8.
    Filippatos GS, Gangopadhyay N, Lalude O, Parameswaran N, Said SI, Spielman W, Uhal BD. 2001. Regulation of apoptosis by vasocactive peptides. Am J Physiol 281:L749–L761.Google Scholar
  9. 9.
    Bkaily G, Choufani S, Hassan G, El-Bizri N, Jacques D, D’Orléans-Juste P. 2000. Presence of functional endothelin-1 receptors in nuclear membranes of human aortic vascular smooth muscle cells. J Cardiovasc Pharmacol 36(Suppl. 1):S414–S417.PubMedGoogle Scholar
  10. 10.
    Gilchrist JSC, Czubryt MP, Pierce GN. 1994. Calcium and calcium-binding proteins in the nucleus. Mol Cell Biochem 135:79–88.PubMedCrossRefGoogle Scholar
  11. 11.
    Bkaily G, Pothier P, D’Orléans-Juste P, Jacques D, Simaan M, Jaalouk D, Belzile F, Hassan G, Boutin F, Haddad G, Neugebauer W. 1997. The use of confocal microscopy in the investigation of cell structure and function in heart, vascular endothelium and smooth muscle cells. Mol Cell Biochem 172:171–194.PubMedCrossRefGoogle Scholar
  12. 12.
    Bkaily G, Massaad D, Choufani S, Jacques D, D’Orléans-Juste P. 2002. Role of endothelin-1 receptors in the sarcolemma membrane and the nuclear membranes in the modulation of basal cytosolic and nuclear calcium levels in heart cells. Clinical Science 103:141–146.Google Scholar
  13. 13.
    Bkaily G, Gros-Louis N, Naik R, Jaalouk D, Pothier P. 1996. Implication of the nucleus in excitation contraction coupling of heart cells. Mol Cell Biochem 154:113–121.PubMedCrossRefGoogle Scholar
  14. 14.
    Bkaily G, D’Orléans-Juste P, Pothier P, Calixto JB, Yuens R. 1997. Nuclear membrane receptors and channel potential therapeutical targets for drug action. Drug Devel Res 42:211–222.CrossRefGoogle Scholar
  15. 15.
    Bkaily G, Jacques D, Pothier P 1999. Use of confocal microscopy to investigate cell structure and function. Methods Enzymol 307:119–135.PubMedCrossRefGoogle Scholar
  16. 16.
    Claing A, Shbaklo H, Plante M, Bkaily G, D’Orléans-Juste P. 2002. Comparison of the contractile and calcium increasing properties of platelet-activating factor and endothelin-1 in the rat mesenteric artery and vein. Br J Pharmacol 135:433–443.PubMedCrossRefGoogle Scholar
  17. 17.
    Bkaily G, Jacques D, Hassan G, Chouffani S, D’Orléans-Juste P. 2001. Using confocal imaging to measure changes in intracellular ions. In: Receptors: Structure and Function. Ed C Stanford and R Horton, 209–231. New York, Oxford University Press.Google Scholar
  18. 18.
    Iborra FJ, Jackson DA, Cook PR. 2001. Coupled transcription and translation within nuclei of mammalian cells. Science 293:1139–1142.PubMedCrossRefGoogle Scholar
  19. 19.
    Al-Mohanna FA, Caddy KWT, Bolsover SR. 1994. The nucleus is insulated from large cytosolic calcium ion changes. Nature 367:745–750.PubMedCrossRefGoogle Scholar
  20. 20.
    Himpsens B, De Smedt H, Casteels R. 1994. Relationship between [Ca2+]i changes in nucleus and cytosol. Cell Calcium 16:239–246.CrossRefGoogle Scholar
  21. 21.
    Jacques D, Sader S, Choufani S, D’Orléans-Juste P, Charest D. 2000. Endothlein-1 regulates cytosolic and nuclear Ca2+ in human endocardial endothelium. J Cardiovasc Pharmacol 36:S397–S400.PubMedGoogle Scholar
  22. 22.
    Cannel MB, Cheng H, Lederer WJ. 1994. Spatial non-uniformities in [Ca]I during excitation contraction coupling in cardiac myocytes. Biophys J 67:1942–1958.CrossRefGoogle Scholar
  23. 23.
    O’Malley DM. 1994. Calcium permeability of the neuronal nuclear envelope: Evaluation using confocal volumes and intracellular perfusion. J Neurosci 14:7541–7558.Google Scholar
  24. 24.
    Santelle L. 1996. The cell nucleus: An eldorado to future calcium research? J Membr Biol 153:83–92.CrossRefGoogle Scholar
  25. 25.
    Haller H, Lindschau C, Quass P, Distler A, Luft FC. 1994. Nuclear calcium signaling is initiated by cytosolic calcium surges in vascular smooth muscle cells. Kidney Int 46:1653–1662.PubMedCrossRefGoogle Scholar
  26. 26.
    Gobeil F, Dumont I, Marrache AM, Vasquez-Tello A, Bernier SG, Arban D, Hou X, Beauchamp MH, Quiniou C, Bouayad A, Choufani S, Bhattacharya M, Molochnikoff S, Ribeiro-da-Silva A, Varma DR, Bkaily G, Chemtob S. Regulation of eNOS expression in brain endothelial cells by perinuclear EP3 receptor. Cir Res 90:682–689.Google Scholar
  27. 27.
    Abrenica B, Gilchrist JSC. 2000. Nucleoplasm Ca2+ loading is regulated by mobilization of perinuclear Ca2+. Cell Calcium 28:127–136.PubMedCrossRefGoogle Scholar
  28. 28.
    Mazzanti M, Bustamante JO, Oberleithner H. 2001. Electrical dimension of nuclear envelope. Pharmacol Rev 81:1–19.Google Scholar
  29. 29.
    Diliberto PA, Krishna S, Kwon S, Herman B. 1994. Isofor-specific induction of nuclear free calcium oscillations by platelet-derived growth factor. J Biol Chem 269:26349–26357.PubMedGoogle Scholar
  30. 30.
    Burnier M, Centeno G, Burki E, Brunner HR. 1994. Confocal microscopy to analyze cytosolic and nuclear calcium in cultured vascular cells. Am J Physiol 266:C1118–C1127.PubMedGoogle Scholar
  31. 31.
    Lin C, Hajnoczky G, Thomas AP. 1994. Propagation of cytosolic calcium waves into the nuclei of hepatocytes. Cell Calcium 16:247–258.PubMedCrossRefGoogle Scholar
  32. 32.
    Carafoli E, Genazzani A, Guerini D. 1999. Calcium signallinig in the cell nucleus. Cell calcium 22:313–319.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2004

Authors and Affiliations

  • Ghassan Bkaily
    • 1
  • Danielle Jacques
    • 2
  • Pedro D’orléans Juste
    • 1
  1. 1.Department of Anatomy and Cell BiologyUSA
  2. 2.Department of Pharmacology, Faculty of MedicineUniversité de SherbrookeSherbrookeCanada

Personalised recommendations