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Regulation of extracellular calcium entry in endothelial cells: role of intracellular calcium pool.

Publication ,  Journal Article
Dolor, RJ; Hurwitz, LM; Mirza, Z; Strauss, HC; Whorton, AR
Published in: Am J Physiol
January 1992

We have investigated the role of the intracellular Ca2+ pool in regulating Ca2+ entry into vascular endothelial cells. The intracellular Ca2+ pool was mobilized using either thapsigargin (TG) or 2',5'-di(tert-butyl)-1,4-benzohydroquinone (BHQ), inhibitors of the endoplasmic reticulum Ca(2+)-adenosinetriphosphatase (ATPase). Mobilization of intracellular Ca2+ stores with either inhibitor depleted intracellular Ca2+ and greatly reduced subsequent mobilization of the inositol 1,4,5-trisphosphate (IP3)-sensitive intracellular Ca2+ pool by bradykinin. However, bradykinin-induced mobilization of the IP3-sensitive intracellular Ca2+ pool only partially reduced the subsequent response of cells to TG and BHQ. Mobilization of the intracellular Ca2+ pool by either TG or BHQ led to a concentration-dependent elevation of cytosolic Ca2+ concentrations ([Ca2+]i) without initiating inositol polyphosphate formation. In contrast to the rapidly developing, transient rise in Ca2+ concentration initiated by bradykinin, maximal concentrations of TG and BHQ stimulated a slowly developing, prolonged elevation of [Ca2+]i that required extracellular Ca2+ and could be blocked by extracellular Ni2+. Extracellular Ca2+ entered the cell through an activated cation entry pathway, since bradykinin, TG, and BHQ stimulated Mn2+ and 45Ca2+ entry. Bradykinin-stimulated 45Ca2+ uptake reached a peak within 2 min, whereas 45Ca2+ influx initiated by TG or BHQ continued for at least 8 min. Importantly, the [Ca2+]i response after low concentrations of BHQ was more transient than that seen after TG. The return of [Ca2+]i to basal values after low concentrations of BHQ was associated with reversal of Ca(2+)-ATPase inhibition and refilling of the IP3-sensitive Ca2+ pool. The continued elevation of [Ca2+]i and prolonged Ca2+ entry seen with TG was associated with continued Ca(2+)-ATPase inhibition and an empty IP3-sensitive Ca2+ pool. We conclude that mobilization of intracellular Ca2+ stores induces Ca2+ entry in endothelial cells which continues until the intracellular Ca2+ pool is refilled.

Duke Scholars

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

January 1992

Volume

262

Issue

1 Pt 1

Start / End Page

C171 / C181

Location

United States

Related Subject Headings

  • Thapsigargin
  • Terpenes
  • Osmolar Concentration
  • Intracellular Membranes
  • Extracellular Space
  • Endothelium, Vascular
  • Cardiovascular System & Hematology
  • Calcium-Transporting ATPases
  • Calcium
  • Bradykinin
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Dolor, R. J., Hurwitz, L. M., Mirza, Z., Strauss, H. C., & Whorton, A. R. (1992). Regulation of extracellular calcium entry in endothelial cells: role of intracellular calcium pool. Am J Physiol, 262(1 Pt 1), C171–C181. https://doi.org/10.1152/ajpcell.1992.262.1.C171
Dolor, R. J., L. M. Hurwitz, Z. Mirza, H. C. Strauss, and A. R. Whorton. “Regulation of extracellular calcium entry in endothelial cells: role of intracellular calcium pool.Am J Physiol 262, no. 1 Pt 1 (January 1992): C171–81. https://doi.org/10.1152/ajpcell.1992.262.1.C171.
Dolor RJ, Hurwitz LM, Mirza Z, Strauss HC, Whorton AR. Regulation of extracellular calcium entry in endothelial cells: role of intracellular calcium pool. Am J Physiol. 1992 Jan;262(1 Pt 1):C171–81.
Dolor, R. J., et al. “Regulation of extracellular calcium entry in endothelial cells: role of intracellular calcium pool.Am J Physiol, vol. 262, no. 1 Pt 1, Jan. 1992, pp. C171–81. Pubmed, doi:10.1152/ajpcell.1992.262.1.C171.
Dolor RJ, Hurwitz LM, Mirza Z, Strauss HC, Whorton AR. Regulation of extracellular calcium entry in endothelial cells: role of intracellular calcium pool. Am J Physiol. 1992 Jan;262(1 Pt 1):C171–C181.

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

January 1992

Volume

262

Issue

1 Pt 1

Start / End Page

C171 / C181

Location

United States

Related Subject Headings

  • Thapsigargin
  • Terpenes
  • Osmolar Concentration
  • Intracellular Membranes
  • Extracellular Space
  • Endothelium, Vascular
  • Cardiovascular System & Hematology
  • Calcium-Transporting ATPases
  • Calcium
  • Bradykinin