Cav3.1 (α1G) controls von Willebrand factor secretion in rat pulmonary microvascular endothelial cells

Chun Zhou, Hairu Chen, Fengmin Lu, Hassan Sellak, Jonathan A. Daigle, Mikhail F. Alexeyev, Yaguang Xi, Jingfang Ju, Jan A. Van Mourik, Songwei Wu

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

The T-type Ca2+ channel Cav3.1 subunit is present in pulmonary microvascular endothelial cells (PMVECs), but not in pulmonary artery endothelial cells (PAECs). The present study sought to assess the role of Cav3.1 in thrombin-induced Weibel-Palade body exocytosis and consequent von Willebrand factor (VWF) release. In PMVECs and PAECs transduced with a green fluorescent protein (GFP)-tagged VWF chimera, we examined the real-time dynamics and secretory process of VWF-GFP-containing vesicles in response to thrombin and the cAMP-elevating agent isoproterenol. Whereas thrombin stimulated a progressive decrease in the number of VWF-GFP-containing vesicles in both cell types, isoproterenol only decreased the number of VWF-GFP-containing vesicles in PAECs. In PMVECs, thrombin-induced decrease in the number of VWF-GFP-containing vesicles was nearly abolished by the T-type Ca2+ channel blocker mibefradil as well as by Cav3.1 gene silencing with small hairpin RNA. Expression of recombinant Cav3.1 subunit in PAECs resulted in pronounced increase in thrombin-stimulated Ca 2+ entry, which is sensitive to mibefradil. Together, these data indicate that VWF secretion from lung endothelial cells is regulated by two distinct pathways involving Ca2+ or cAMP, and support the hypothesis that activation of Cav3.1 T-type Ca2+ channels in PMVECs provides a unique cytosolic Ca2+ source important for G q-linked agonist-induced VWF release.

Original languageEnglish (US)
Pages (from-to)L833-L844
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume292
Issue number4
DOIs
StatePublished - Apr 1 2007

Keywords

  • Endothelial cells
  • Thrombin

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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    Zhou, C., Chen, H., Lu, F., Sellak, H., Daigle, J. A., Alexeyev, M. F., Xi, Y., Ju, J., Van Mourik, J. A., & Wu, S. (2007). Cav3.1 (α1G) controls von Willebrand factor secretion in rat pulmonary microvascular endothelial cells. American Journal of Physiology - Lung Cellular and Molecular Physiology, 292(4), L833-L844. https://doi.org/10.1152/ajplung.00377.2006