Ca v 3.1 (α 1G ) T-Type Ca 2+ Channels Mediate Vaso-Occlusion of Sickled Erythrocytes in Lung Microcirculation

Abstract

In the present study, we demonstrate that lung microvascular endothelial cells express a Ca_v3.1 (α_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.