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Activation of TRPV4 increases endothelial permeability in lung septal capillaries
Author(s) -
Alvarez Diego F.,
King Judy A.,
Liedtke Wolfgang,
Townsley Mary I.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a747-c
Subject(s) - trpv4 , chemistry , lung , vascular permeability , permeability (electromagnetism) , transient receptor potential channel , wild type , medicine , anatomy , endocrinology , biophysics , receptor , biology , biochemistry , mutant , membrane , gene
Activation of store‐operated Ca 2+ channels disrupts endothelial cell (EC) junctions in lung extra‐alveolar vessels, while the channel responsible for Ca 2+ entry‐dependent injury in septal capillaries is unknown. Since 14,15‐epoxyeicosatrienoic acid (14,15‐EET) causes EC injury in rat lung septal capillaries and EETs activate Ca 2+ entry via the vanilloid transient receptor potential channel TRPV4 in aortic EC, we tested whether activation of TRPV4 increases septal EC permeability. Lungs from anesthetized wild type mice (TRPV4 +/+ ) and null littermates (TRPV4 −/− ) (22.2±0.9 g, mean±SE) were perfused at 0.055±0.002 mL/min/g body wt with 4% albumin/physiologic buffer (37 °C). EC permeability was measured via the filtration coefficient (K f ) at baseline and 45 min after treatment with 4α‐phorbol‐12,13‐didecanoate (4αPDD, 10 μM) to activate TRPV4, thapsigargin (TG, 150 nM) to activate store‐operated Ca 2+ channels, or vehicle (DMSO, 50 μL). TG increased permeability by 2.8‐ and 3.2‐fold in wild type and null groups, respectively (*p<0.05, paired t‐test). In contrast, 4αPDD increased permeability by 2.9‐fold in lungs from TRPV4 +/+ mice, but had no impact in TRPV4 −/− mice. Transmissionelectron microscopy revealed that 4αPDD resulted in blebbing of septal EC in wild type mice while extra‐alveolar vessel EC junctions were intact, a pattern similar to that with 14,15‐EET in rat lung. We conclude that TRPV4 constitutes a novel Ca 2+ entry pathway involved in regulation of lung EC permeability in septal capillaries.Supported by HL081851 and SE AHA 0315049B.