CaV3.1 (α1G) T-type Ca2+ channels mediate vaso-occlusion of sickled erythrocytes in lung microcirculation

Academic Article

Abstract

  • In the present study, we demonstrate that lung microvascular endothelial cells express a Ca 3.1 (α ) T-type voltage-gated Ca channel, whereas lung macrovascular endothelial cells do not express voltage-gated Ca channels. Voltage-dependent activation indicates that the Ca 3.1 T-type Ca current is shifted to a positive potential, at which maximum current activation is -10 mV; voltage-dependent conductance and inactivation properties suggest a "window current" in the range of -60 to -30 mV. Thrombin-induced transitions in membrane potential activate the Ca 3.1 channel, resulting in a physiologically relevant rise in cytosolic Ca . Furthermore, activation of the Ca 3.1 channel induces a procoagulant endothelial phenotype; eg, channel inhibition attenuates increased retention of sickled erythrocytes in the inflamed pulmonary circulation. We conclude that activation of the Ca 3.1 channels selectively induces phenotypic changes in microvascular endothelial cells that mediate vaso-occlusion by sickled erythrocytes in the inflamed lung microcirculation. v 1G v v v v 2+ 2+ 2+ 2+
  • Authors

    Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 17449003
  • Author List

  • Wu S; Haynes J; Taylor JT; Obiako BO; Stubbs JR; Li M; Stevens T
  • Start Page

  • 346
  • End Page

  • 353
  • Volume

  • 93
  • Issue

  • 4