Wu, Songwei Jian, Ming-Yuan Xu, Yan-Chun Zhou, Chun Al-Mehdi, Abu-Bakr Liedtke, Wolfgang Shin, Hee-Sup Townsley, Mary I. 2024-01-20T20:34:08Z 2024-01-20T20:34:08Z 2021-09-04 2009-10 1040-0605 https://pubs.kist.re.kr/handle/201004/132132 Wu S, Jian MY, Xu YC, Zhou C, Al-Mehdi AB, Liedtke W, Shin HS, Townsley MI. 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 297: L650-L657, 2009. First published July 17, 2009; doi:10.1152/ajplung.00015.2009.-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 alpha(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 alpha-phorbol-12,13-didecanoate (4 alpha-PDD) specifically increases lung endothelial permeability without effect on P-selectin expression. Pharmacological blockade or knockout of alpha(1G) abolishes depolarization-induced Ca2+ entry and surface expression of P-selectin but does not prevent 4 alpha-PDD-activated Ca2+ entry and the resultant increase in permeability. Conversely, blockade or knockout of TRPV4 specifically abolishes 4 alpha-PDD-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 alpha(1G) and TRPV4 channels differentially and specifically regulates the transition of endothelial procoagulant phenotype and barrier integrity, respectively. English AMER PHYSIOLOGICAL SOC INDUCED LUNG INJURY PHENOTYPIC HETEROGENEITY ION CHANNELS VASCULAR ENDOTHELIUM RAT LUNG PERMEABILITY CELL ISCHEMIA MICE RESISTANCE Ca2+ entry via alpha(1G) and TRPV4 channels differentially regulates surface expression of P-selectin and barrier integrity in pulmonary capillary endothelium Article 10.1152/ajplung.00015.2009 1 AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, v.297, no.4, pp.L650 - L657 AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 297 4 L650 L657 scie scopus 000270186800011 2-s2.0-70349773183 Physiology Respiratory System Physiology Respiratory System Article INDUCED LUNG INJURY PHENOTYPIC HETEROGENEITY ION CHANNELS VASCULAR ENDOTHELIUM RAT LUNG PERMEABILITY CELL ISCHEMIA MICE RESISTANCE T-type calcium channel transient receptor potential vanilloid 4 vascular permeability