Epithelial Na⁺ channel proteins are mechanotransducers of myogenic constriction in rat posterior cerebral arteries

Abstract

It has been suggested that mechanosensitive ion channels initiate myogenic responses in vessels; however, the molecular identity of the mechanosensitive ion channel complex is unknown. Although previous reports have suggested that epithelial Na + channel (ENaC) proteins are mechanotransducers in arteries, experimental evidence demonstrating that ENaC proteins are mechanotransducers are not fully elucidated. The goal of the present study was to determine whether the ENaC is a mechanotransducer for the myogenic response by providing supporting evidence in the rat posterior cerebral artery (PCA). We measured the effect of ENaC inhibition on the pressure-induced myogenic response, Ca

Renal Autoregulation in Health and Disease

“…DEG-like currents in cerebral arterial VSMCs were inhibited by ROS (257). ␤-ENaC in rat posterior cerebral arteries colocalized with TRPM4 but not TRPC6 (793,794), although all three channels participated in myogenic constriction.…”

“…zamil (1 M) or siRNA knockdown of ␤-or ␥-ENaC subunits attenuated some of the myogenic constriction in rat posterior cerebral arteries (793). Myogenic constriction of middle cerebral arteries of ASIC2 knockout mice was very weak, whereas constrictor responses to high KCl and PE were normal, suggesting specificity to mechanical stimulation (454).…”

Regulator of G Protein Signaling 2

“…Myogenic response evoked by stretch of smooth muscle cells depends on activation of stretch receptors mediating mechanotransduction signaling[50, 51]. Although the components of this signaling mechanism in smooth muscle remain to be fully defined, receptors studied to date include members of the transient receptor potential (TRP) superfamily[52], vascular epithelial sodium channel (ENaC)[53], integrins[54], and the angiotensin type 1 receptor (AT1R)[55]. Whereas RGS2 is known to negatively regulate vascular AT1R signaling, it remains possible that RGS2 regulates other mediators of vascular mechanotransduction (Figure 2) that are not known to couple to heterotrimeric G proteins.…”

Blockade of ENaCs by amiloride induces c-Fos activation of the area postrema

“…ENaCs present in the choroid plexus regulate the [Na + ] of the cerebrospinal fluid (Amin et al, 2009; Nakano et al, 2013; Wang et al, 2010). ENaCs expressed in brain endothelial cells function much like those found in peripheral endothelial cells (Kim et al, 2012; Kusche-Vihrog et al, 2013), serving to stiffen mechanically these cells and trigger the release of the nitric oxide which acts on its underlying smooth muscle to induce local vasodilation (Kusche-Vihrog et al, 2013). However, the role of ENaCs that are expressed in astrocytes (Miller and Loewy, 2013) and neurons (Amin et al, 2005; Miller et al, 2013; Teruyama et al, 2012) remains elusive.…”