Ca2+ Entry via α1G and TRPV4 Channels Differentially Regulates Surface Expression of P-selectin and Barrier Integrity in Pulmonary Capillary Endothelium
- Ca2+ Entry via α1G and TRPV4 Channels Differentially Regulates Surface Expression of P-selectin and Barrier Integrity in Pulmonary Capillary Endothelium
- Wu S; Jian MY; Xu YC; Zhou C; Al-Mehdi AB; Liedtke W; 신희섭; Townsley MI
- Issue Date
- American journal of physiology. Lung cellular and molecular physiology
- VOL 297, NO 4, L650-L657
- Pulmonary vascular endothelial cells express a variety of ion channels that mediate Ca2+ influx in response to diverse environmental stimuli. However, it is not clear whether Ca2+ influx from discrete ion channels is functionally coupled to specific outcomes. Thus, we conducted a systematic study in mouse lung to address whether the 1G T-type Ca2+ channel and the transient receptor potential channel TRPV4 have discrete functional roles in pulmonary capillary endothelium. We used real-time fluorescence imaging for endothelial cytosolic Ca2+, immunohistochemistry to probe for surface expression of P-selectin and the filtration coefficient to specifically measure lung endothelial permeability. We demonstrate that membrane depolarization via exposure of pulmonary vascular endothelium to a high K+ perfusate induces Ca2+ entry into alveolar septal endothelial cells and exclusively leads to the surface expression of P-selectin. In contrast, Ca2+ entry in septal endothelium evoked by the selective TRPV4-activator 4-phorbol-12,13-didecanoate (4PDD) specifically increases lung endothelial permeability without effect on P-selectin expression. Pharmacologic blockade or knockout of 1G abolishes depolarization-induced Ca2+ entry and surface expression of P-selectin, but does not prevent 4PDD-activated Ca2+ entry and the resultant increase in permeability. Conversely, blockade or knockout of TRPV4 specifically abolishes 4PDD-activated Ca2+ entry and the increase in permeability, while not impacting depolarization-induced Ca2+ entry and surface expression of P-selectin. We conclude that in alveolar septal capillaries, Ca2+ entry through 1G and TRPV4 channels differentially and specifically regulates the transition of endothelial procoagulant phenotype and barrier integrity, respectively.
- Appears in Collections:
- KIST Publication > Article
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.