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Emerging roles of calcium‐activated K channels and TRPV 4 channels in lung oedema and pulmonary circulatory collapse
Author(s) -
Simonsen U.,
WandallFrostholm C.,
OlivánViguera A.,
Köhler R.
Publication year - 2017
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12768
Subject(s) - trpv4 , transient receptor potential channel , vasodilation , circulatory system , lung , medicine , extravasation , endothelium , nitric oxide , chemistry , anesthesia , pathology , receptor
It has been suggested that the transient receptor potential cation ( TRP ) channel subfamily V (vanilloid) type 4 ( TRPV 4) and intermediate conductance calcium‐activated potassium ( KC a3.1) channels contribute to endothelium‐dependent vasodilation. Here, we summarize very recent evidence for a synergistic interplay of TRPV 4 and KC a3.1 channels in lung disease. Among the endothelial Ca 2+ ‐permeable TRP s, TRPV 4 is best characterized and produces arterial dilation by stimulating Ca 2+ ‐dependent nitric oxide synthesis and endothelium‐dependent hyperpolarization. Besides these roles, some TRP channels control endothelial/epithelial barrier functions and vascular integrity, while KC a3.1 channels provide the driving force required for Cl − and water transport in some cells and most secretory epithelia. The three conditions, increased pulmonary venous pressure caused by left heart disease, high inflation pressure and chemically induced lung injury, may lead to activation of TRPV 4 channels followed by Ca 2+ influx leading to activation of KC a3.1 channels in endothelial cells ultimately leading to acute lung injury. We find that a deficiency in KC a3.1 channels protects against TRPV 4‐induced pulmonary arterial relaxation, fluid extravasation, haemorrhage, pulmonary circulatory collapse and cardiac arrest in vivo . These data identify KC a3.1 channels as crucial molecular components in downstream TRPV 4 signal transduction and as a potential target for the prevention of undesired fluid extravasation, vasodilatation and pulmonary circulatory collapse.