This Article Full Text Full Text (PDF) All Versions of this Article: 93/4/346    most recent 01.RES.0000087148.75363.8Fv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, S. Articles by Stevens, T. Search for Related Content PubMed PubMed Citation Articles by Wu, S. Articles by Stevens, T. Related Collections Calcium cycling/excitation-contraction coupling Endothelium/vascular type/nitric oxide

(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

This article has been cited by other articles:

				S. Wu, M.-Y. Jian, Y.-C. Xu, C. Zhou, A.-B. Al-Mehdi, W. Liedtke, H.-S. Shin, and M. I. Townsley Ca2+ entry via {alpha}1G and TRPV4 channels differentially regulates surface expression of P-selectin and barrier integrity in pulmonary capillary endothelium Am J Physiol Lung Cell Mol Physiol, October 1, 2009; 297(4): L650 - L657. [Abstract] [Full Text] [PDF]

				A. Moldobaeva, J. Jenkins, and E. Wagner Effects of distension on airway inflammation and venular P-selectin expression Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L941 - L948. [Abstract] [Full Text] [PDF]

				D. J. Metcalf, T. D. Nightingale, H. L. Zenner, W. W. Lui-Roberts, and D. F. Cutler Formation and function of Weibel-Palade bodies J. Cell Sci., January 1, 2008; 121(1): 19 - 27. [Abstract] [Full Text] [PDF]

				M. L. Paffett, J. S. Naik, T. C. Resta, and B. R. Walker Reduced store-operated Ca2+ entry in pulmonary endothelial cells from chronically hypoxic rats Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1135 - L1142. [Abstract] [Full Text] [PDF]

				X. F. Figueroa, C.-C. Chen, K. P. Campbell, D. N. Damon, K. H. Day, S. Ramos, and B. R. Duling Are voltage-dependent ion channels involved in the endothelial cell control of vasomotor tone? Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1371 - H1383. [Abstract] [Full Text] [PDF]

				C. Zhou, H. Chen, F. Lu, H. Sellak, J. A. Daigle, M. F. Alexeyev, Y. Xi, J. Ju, J. A. van Mourik, and S. Wu Cav3.1 ({alpha}1G) controls von Willebrand factor secretion in rat pulmonary microvascular endothelial cells Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L833 - L844. [Abstract] [Full Text] [PDF]

				T. R. Uhrenholt, T. L. Domeier, and S. S. Segal Propagation of calcium waves along endothelium of hamster feed arteries Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1634 - H1640. [Abstract] [Full Text] [PDF]

				S. Wu, E. A. Cioffi, D. Alvarez, S. L. Sayner, H. Chen, D. L. Cioffi, J. King, J. R. Creighton, M. Townsley, S. R. Goodman, et al. Essential Role of a Ca2+-Selective, Store-Operated Current (ISOC) in Endothelial Cell Permeability: Determinants of the Vascular Leak Site Circ. Res., April 29, 2005; 96(8): 856 - 863. [Abstract] [Full Text] [PDF]

				V. Pastukh, S. Wu, C. Ricci, M. Mozaffari, and S. Schaffer Reversal of hyperglycemic preconditioning by angiotensin II: role of calcium transport Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1965 - H1975. [Abstract] [Full Text] [PDF]

				P. A. Lang, D. S. Kempe, V. Tanneur, K. Eisele, B. A. Klarl, S. Myssina, V. Jendrossek, S. Ishii, T. Shimizu, M. Waidmann, et al. Stimulation of erythrocyte ceramide formation by platelet-activating factor J. Cell Sci., March 15, 2005; 118(6): 1233 - 1243. [Abstract] [Full Text] [PDF]

				X. F. Figueroa, B. E. Isakson, and B. R. Duling Connexins: Gaps in Our Knowledge of Vascular Function Physiology, October 1, 2004; 19(5): 277 - 284. [Abstract] [Full Text] [PDF]

				A. Varghese and E. K. Weir T-Type Calcium Current in Sickle Cell Disease: A Channel to Therapy? Circ. Res., August 22, 2003; 93(4): 274 - 276. [Full Text] [PDF]