000079328 001__ 79328
000079328 005__ 20190709135652.0
000079328 0247_ $$2doi$$a10.1111/apha.12768
000079328 0248_ $$2sideral$$a103204
000079328 037__ $$aART-2017-103204
000079328 041__ $$aeng
000079328 100__ $$aSimonsen, Ulf
000079328 245__ $$aEmerging roles of calcium-activated K channels and TRPV4 channels in lung oedema and pulmonary circulatory collapse
000079328 260__ $$c2017
000079328 5060_ $$aAccess copy available to the general public$$fUnrestricted
000079328 5203_ $$aIt has been suggested that the transient receptor potential cation (TRP) channel subfamily V (vanilloid) type 4 (TRPV4) and intermediate conductance calcium-activated potassium (KCa3.1) channels contribute to endothelium-dependent vasodilation. Here, we summarize very recent evidence for a synergistic interplay of TRPV4 and KCa3.1 channels in lung disease. Among the endothelial Ca2+-permeable TRPs, TRPV4 is best characterized and produces arterial dilation by stimulating Ca2+-dependent nitric oxide synthesis and endothelium-dependent hyperpolarization. Besides these roles, some TRP channels control endothelial/epithelial barrier functions and vascular integrity, while KCa3.1 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 TRPV4 channels followed by Ca2+ influx leading to activation of KCa3.1 channels in endothelial cells ultimately leading to acute lung injury. We find that a deficiency in KCa3.1 channels protects against TRPV4-induced pulmonary arterial relaxation, fluid extravasation, haemorrhage, pulmonary circulatory collapse and cardiac arrest in vivo. These data identify KCa3.1 channels as crucial molecular components in downstream TRPV4 signal transduction and as a potential target for the prevention of undesired fluid extravasation, vasodilatation and pulmonary circulatory collapse.
000079328 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000079328 590__ $$a5.93$$b2017
000079328 591__ $$aPHYSIOLOGY$$b5 / 83 = 0.06$$c2017$$dQ1$$eT1
000079328 592__ $$a1.542$$b2017
000079328 593__ $$aPhysiology$$c2017$$dQ1
000079328 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000079328 700__ $$aWandall-Frostholm, Christinne
000079328 700__ $$0(orcid)0000-0001-5348-924X$$aOliván-Viguera, Aida
000079328 700__ $$0(orcid)0000-0002-0833-9717$$aKöhler, Ralf
000079328 773__ $$g219, 1 (2017), 176-187 [29 p.]$$pActa Physiol.$$tActa Physiologica$$x1748-1708
000079328 8564_ $$s300040$$uhttps://zaguan.unizar.es/record/79328/files/texto_completo.pdf$$yPostprint
000079328 8564_ $$s60529$$uhttps://zaguan.unizar.es/record/79328/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000079328 909CO $$ooai:zaguan.unizar.es:79328$$particulos$$pdriver
000079328 951__ $$a2019-07-09-12:44:01
000079328 980__ $$aARTICLE