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(Circulation Research. 2003;93:346.)
© 2003 American Heart Association, Inc.

Cellular Biology

Ca_v3.1 (_1G) T-Type Ca²⁺ Channels Mediate Vaso-Occlusion of Sickled Erythrocytes in Lung Microcirculation

Songwei Wu, Johnson Haynes, Jr, James T. Taylor, Boniface O. Obiako, James R. Stubbs, Ming Li, Troy Stevens

From the Departments of Pharmacology (S.W., T.S.), Medicine (J.H.), and Pathology (J.R.S.), the Center for Lung Biology (S.W., J.H., T.S.), and the Comprehensive Sickle Cell Center (J.H., B.O.O.), University of South Alabama College of Medicine, Mobile, Ala, and the Department of Pharmacology (J.T.T., M.L.), Tulane University School of Medicine, New Orleans, La.

Correspondence to Songwei Wu, MD, Center for Lung Biology and Department of Pharmacology, MSB 3370, University of South Alabama College of Medicine, Mobile, AL 36688. E-mail swu{at}jaguar1.usouthal.edu

In the present study, we demonstrate that lung microvascular endothelial cells express a Ca_v3.1 (_1G) T-type voltage-gated Ca²⁺ channel, whereas lung macrovascular endothelial cells do not express voltage-gated Ca²⁺ channels. Voltage-dependent activation indicates that the Ca_v3.1 T-type Ca²⁺ 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_v3.1 channel, resulting in a physiologically relevant rise in cytosolic Ca²⁺. Furthermore, activation of the Ca_v3.1 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_v3.1 channels selectively induces phenotypic changes in microvascular endothelial cells that mediate vaso-occlusion by sickled erythrocytes in the inflamed lung microcirculation.

Key Words: endothelial cells • store-operated Ca²⁺ entry • P-selectin • von Willebrand factor • coagulation

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