Critical role of TRPP2 and TRPC1 channels in stretch-induced injury of blood–brain barrier endothelial cells

Update on vascular endothelial Ca2+signalling: A tale of ion channels, pumps and transporters

“…Shear-stress-induced and TRPP1/TRPP2-dependent Ca 2+ entry, in turn, triggers NO production by recruiting PKC, Ca 2+ -calmodulin and the PI3K/Akt pathway [332,333] . Moreover, TRPP2 may aid TRPC1 in mediating Ca 2+ influx, NO production, and actin reorganization in bEnd3 cells exposed to mechanical stress [229] , as aforementioned.…”

“…In addition, such an enhanced vesicular trafficking of TRPC1-TRPV4 channels may contribute to endothelial SOCs [228] . Similarly, TRPC1 may mediate stretch-induced Ca 2+ entry after traumatic injury in microvessel endothelial cells, thereby resulting in NO synthesis and actin stress fiber formation [229] . TRPC3/6/7: TRPC3, TRPC6 and TRPC7 are Ca 2+ -permeable channels that may be activated by DAG in a PKC-independent manner and may thus be regarded as SMOCs [200,201] .…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…By contrast, there is no doubt that TRPC1 can form functional heteromers with other TRPC channels 682 Storch et al, 2012), with TRPV4 , and probably also with ORAI1 (a Ca 2+ release-activated calcium channel protein), forming store-operated channels Cioffi et al, 2010Cioffi et al, , 2012. In microvessels, TRPC1 together with TRPP1 [polycystic kidney disease (PKD)-2, also referred to as PC2] controls the blood-brain barrier (Berrout et al, 2012). It has been reported that TRPC1 may play a role in smooth muscle contraction (Xu and Beech, 2001), osteoclast formation (Ong et al, 2013), and control of cell migration (Fabian et al, 2008) and is involved in BDNF-and netrin-1-induced axon guidance (Wang and Poo, 2005; for review, see Nilius et al, 2007b;Gees et al, 2012).…”

Polycystins and mechanotransduction: From physiology to disease

“…Similarly, in the heart, PC2 interacts with the ryanodine receptor RyR2 via its Cterminus to modulate release of Ca 2+ from the SR stores [33] . Notably, PC2 can form a channel with TRPC1, being activated in response to mechanical damage of blood brain barrier endothelial cells by promoting Ca 2+ influx and formation of actin stress fibers [12] . Finally, in vascular smooth muscle cells PC2 has been implicated in sensing pressure volume and in mesenteric and cerebral arteries in sensing myogenic tone [19,34] .…”

“…Polycystins are implicated in renal flow sensing [8] , vascular pressure and flow mechanosensation [911] , bloodbrain barrier mechanical injury [12] , nodal flow sensing [13] , skeletal development and osteoblast differentiation [14,15] as well as cancer progression [16] .…”