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The amiloride-sensitive endothelial sodium channel and vascular tone.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Warnock, David |
| Copyright Year | 2013 |
| Abstract | See related article, pp 1053–1059 In this issue of Hypertension , Jeggle et al1 provide important new insights into the characteristics and functional significance of an amiloride-sensitive sodium channel that is expressed in vascular endothelial cells. This work extends the previous analyses by this group,2,3 and using atomic force microscopy and state-of-the art animal and cell models, provides provocative yet conclusive evidence for the central role of this channel in regulation vascular reactivity and stiffness. The Figure depicts the heteromeric structure of the amiloride-sensitive sodium channel. Although the overall topology of the channel is well described,4 there is no general agreement about the subunit composition even within epithelial cells, much less in other tissues like vascular endothelial cells that are the subject of the current report. The bulk of the subunits’ structures are expressed in the intertwined disulfide-rich extracellular domains, the role of which has not been fully explained. The subunits of the epithelial sodium channel (ENaC) were originally defined by now-classical expression cloning studies by Canessa and Rossier.5 The human genomic clones and the critical insight into the gain of function effect that characterizes Liddle syndrome6 was based on analogy to defects in the mechanosensor structures of degenerins in Caenorhabditis elegans .7 Although longitudinal flow is certainly a feature of many epithelial tubule systems, a direct connection among the putative mechanical transduction function, the extracellular domains, and regulation of apical sodium entry via ENaC is not obvious. In contrast, there are pulsatile pressures and flows in the systemic vascular system. Local regulation of vascular tone in response to changes in pressure and shear stress, an important feature of the microvascular circulation, lending credance to the idea that the extensive extracellular of the vascular endothelial … |
| File Format | PDF HTM / HTML |
| DOI | 10.1161/HYPERTENSIONAHA.113.00768 |
| PubMed reference number | 23460291 |
| Journal | Medline |
| Volume Number | 61 |
| Issue Number | 5 |
| Alternate Webpage(s) | http://hyper.ahajournals.org/content/hypertensionaha/61/5/952.full.pdf?download=true |
| Alternate Webpage(s) | https://doi.org/10.1161/HYPERTENSIONAHA.113.00768 |
| Journal | Hypertension |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
