βENaC is required for whole cell mechanically gated currents in renal vascular smooth muscle cells

Chung, Wen-Shuo; Weissman, Jennifer L.; Farley, Jerry M.; Drummond, Heather A.

doi:10.1152/ajprenal.00444.2012

Cited by 22 publications

(13 citation statements)

References 44 publications

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“…For example, mechano-activated whole cell Na + currents have been described in vascular smooth muscle cells. 168 These currents were reduced when β subunit expression was reduced, but it is not known if these mechano-activated whole cell currents are amiloride sensitive. Vascular smooth muscle cells also express ASIC subunits, and it has been suggested that the mechano-sensory channel complexes might be composed of a combination of ENaC and ASIC subunits.…”

Section: Expression and Regulation Of Amiloride-sensitive Na+ Channelmentioning

confidence: 99%

Blood pressure and amiloride-sensitive sodium channels in vascular and renal cells

et al. 2014

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This review is focused on the expression and regulation of amiloride-sensitive sodium channels in the epithelial cells of the aldosterone-sensitive distal nephron (ENaC) and amiloride-sensitive sodium channel activity in vascular endothelial and smooth muscle cells. Guyton’s hypothesis stated that blood pressure control is critically dependent on vascular tone and fluid handling by the kidney. With the study of Mendelian forms of hypertension and their corresponding transgenic mouse models, the main components of the aldosterone- and angiotensin-dependent sodium transporters have been identified over the past 20 years. Proteolytic processing of the ENaC external domain, and inhibition by increased sodium concentrations are important features of the ENaC complexes expressed in the distal nephron. In contrast, amiloride-sensitive sodium channels expressed in the vascular system are activated by increased external sodium concentrations, resulting in changes in the mechanical properties and function of endothelial cells. Mechano-sensitivity and shear stress affect both epithelial and vascular sodium channel activity. The synergistic effects and complementary regulation of the epithelial and vascular systems are consistent with the Guytonian model of volume and blood pressure regulation, and may reflect sequential evolution of the two systems. The integration of vascular tone, renal perfusion and regulation of renal sodium reabsorption is the central underpinning of the Guytonian model. We summarize the recent evidence in this review that describes the central role of amiloride-sensitive sodium channels in the efferent (e.g., vascular) and afferent (e.g., epithelial) arms of this homeostatic system.

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Section: Expression and Regulation Of Amiloride-sensitive Na+ Channelmentioning

confidence: 99%

Blood pressure and amiloride-sensitive sodium channels in vascular and renal cells

et al. 2014

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“…In addition, β and γ ENaC, but not α ENaC, were identified in vascular smooth muscle cells of renal arteries, where they contribute to pressure-induced vasoconstriction (Drummond, 2007(Drummond, , 2012. Other studies provided evidence that β ENaC is essential for regulating renal arterial myogenic tone in vitro and in vivo (Chung et al, 2013). The findings in renal arteries highlight the importance of the β ENaC subunit for mechanosensation.…”

Section: Introductionmentioning

confidence: 95%

Epithelial Na+ Channel (ENaC) Formed by One or Two Subunits Forms Functional Channels That Respond to Shear Force

2020

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Canonical epithelial sodium channels (ENaCs) are heterotrimers formed by α, β, and γ ENaC subunits in vertebrates and belong to the Degenerin/ENaC family of proteins. Proteins from this family form mechanosensitive channels throughout the animal kingdom. Activity of canonical ENaC is regulated by shear force (SF) mediating Na + absorption in the kidney and vascular tone of arteries. Expression analysis suggests that non-canonical ENaC, formed by single or only two subunits, exist in certain tissues, but it is unknown if these channels respond to SF. α, β, γ, and δ ENaC subunits were expressed either alone or in combinations of two subunits in Xenopus oocytes. Amiloride-sensitive currents and the responses to SF were assessed using two-electrode voltage clamp recordings. With the exception of γ ENaC, all homomeric channels provided amiloride-sensitive currents and responded to SF applied via a fluid stream directed onto the oocytes. Channels containing two subunits were also activated by SF. Here, the presence of the γ ENaC subunit when co-expressed with α or δ augmented the SF response in comparison to the αβγ/δβγ ENaC. Overall, we provide evidence that non-canonical ENaC can form channels that respond to SF. This supports a potential function of non-canonical ENaC as mechanosensors in epithelial, vascular, and sensory cells.

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“…Since the importance of strain/stretch in activating a mammalian degenerin has not been addressed, our laboratory developed a novel in-vitro electrophysiologic assay to assess mechanically gated currents in isolated VSMCs using stretch (17). Briefly, enzymatically dissociated renal VSMCs are plated on an elasmoteric substrate coated with collagen.…”

Section: Do Degenerin Proteins Mediate Mechanically Gated Currents?mentioning

confidence: 99%

βENaC Acts as a Mechanosensor in Renal Vascular Smooth Muscle Cells That Contributes to Renal Myogenic Blood Flow Regulation, Protection From Renal Injury and Hypertension

Drummond

Stec

2015

Journal of Nephrology Research

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Pressure-induced constriction (also known as the “myogenic response”) is an important mechanodependent response in small renal arteries and arterioles. The response is initiated by vascular smooth muscle cell (VSMC) stretch due to an increase in intraluminal pressure and leads to vasoconstriction. The myogenic response has two important roles as a mechanism of local blood flow autoregulation and protection against systemic blood pressure-induced microvascular damage. However, the molecular mechanisms underlying initiation of myogenic response are unresolved. Although several molecules have been considered initiators of the response, our laboratory has focused on the role of degenerin proteins because of their strong evolutionary link to mechanosensing in the nematode. Our laboratory has addressed the hypothesis that certain degenerin proteins act as mechanosensors in VSMCs. This article discusses the importance of a specific degenerin protein, β Epithelial Na+ Channel (βENaC), in pressure-induced vasoconstriction, renal blood flow and susceptibility to renal injury. We propose that loss of the renal myogenic constrictor response delays the correction of renal blood flow that occurs with fluctuations in systemic pressure, which allows pressure swings to be transmitted to the microvasculature, thus increasing the susceptibility to renal injury and hypertension. The role of βENaC in myogenic regulation is independent of tubular βENaC and thus represents a non-tubular role for βENaC in renal-cardiovascular homeostasis.

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βENaC is required for whole cell mechanically gated currents in renal vascular smooth muscle cells

Cited by 22 publications

References 44 publications

Blood pressure and amiloride-sensitive sodium channels in vascular and renal cells

Blood pressure and amiloride-sensitive sodium channels in vascular and renal cells

Epithelial Na+ Channel (ENaC) Formed by One or Two Subunits Forms Functional Channels That Respond to Shear Force

βENaC Acts as a Mechanosensor in Renal Vascular Smooth Muscle Cells That Contributes to Renal Myogenic Blood Flow Regulation, Protection From Renal Injury and Hypertension

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