Epithelial Na+ Channels Are Activated by Laminar Shear Stress

Carattino, Marcelo D.; Sheng, Shaohu; Kleyman, Thomas R.

doi:10.1074/jbc.m311783200

Cited by 143 publications

(160 citation statements)

References 35 publications

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“…Ferguson and coworkers previously proposed that ENaC may act as a mechanosensor to regulate ATP release from the uroepithelium (Ferguson, 1999), and data from other cell types indicates that ENaC activity may be triggered by membrane stretch (Lewis and de Moura, 1982;Ferguson et al, 1997;Carattino et al, 2004;Althaus et al, 2007). Our data indicate that ENaC, acting downstream or in conjunction with the NSCC, could play a role in mechanotransduction by modulating membrane potential or cross-talk between ion channels at the apical and basolateral membrane domains.…”

Section: Regulation Of Umbrella Cell Apical Membrane Traffic By Ion Csupporting

confidence: 54%

Distinct Apical and Basolateral Membrane Requirements for Stretch-induced Membrane Traffic at the Apical Surface of Bladder Umbrella Cells

Khandelwal²,

Apodaca

2009

MBoC

127

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Epithelial cells respond to mechanical stimuli by increasing exocytosis, endocytosis, and ion transport, but how these processes are initiated and coordinated and the mechanotransduction pathways involved are not well understood. We observed that in response to a dynamic mechanical environment, increased apical membrane tension, but not pressure, stimulated apical membrane exocytosis and ion transport in bladder umbrella cells. The exocytic response was independent of temperature but required the cytoskeleton and the activity of a nonselective cation channel and the epithelial sodium channel. The subsequent increase in basolateral membrane tension had the opposite effect and triggered the compensatory endocytosis of added apical membrane, which was modulated by opening of basolateral K ؉ channels. Our results indicate that during the dynamic processes of bladder filling and voiding apical membrane dynamics depend on sequential and coordinated mechanotransduction events at both membrane domains of the umbrella cell.

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Section: Regulation Of Umbrella Cell Apical Membrane Traffic By Ion Csupporting

confidence: 54%

Distinct Apical and Basolateral Membrane Requirements for Stretch-induced Membrane Traffic at the Apical Surface of Bladder Umbrella Cells

Khandelwal²,

Apodaca

2009

MBoC

127

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“…Whereas the location and nature of the ENaC gate and mechanisms by which signals are transmitted to alter channel openings and closures have not been defined, analyses of ENaC mutants have shown that multiple regions within ENaC influence channel gating (1,(13)(14)(15)(16)(17). Previous studies have shown that selected mutations within the pre-M2 tract have dramatic effects on channel gating (18,22).…”

Section: Resultsmentioning

confidence: 99%

“…The recording chamber was perfused at a rate of 3.5 ml/min. Laminar shear stress was applied by perfusing TEV solution through a vertical pipette localized above the oocyte surface at a rate of 1.6 ml/min, corresponding to 0.137 dynes/cm 2 of shear stress as described previously (13). Bath perfusion was maintained during application of LSS.…”

Section: Methodsmentioning

confidence: 99%

“…We recently demonstrated that laminar fluid perfusion of oocytes expressing ENaCs resulted in a flow-dependent increase in whole cell Na ϩ currents. Furthermore, mutant channels (␣␤S518K␥ or ␣S580C␤␥ following modification by a specific sulfhydryl reagent) that are known to exhibit a high intrinsic open probability did not respond to laminar shear stress (LSS), suggesting that LSS activates ENaC by increasing channel open probability (13).…”

mentioning

confidence: 99%

“…Degenerin/ENaC channels with mutations within either (i) a region preceding the second membrane-spanning domain (pre-M2), (ii) the extracellular loop, (iii) the N-or (iv) C-terminal domains alter channel openings and closures (1,(13)(14)(15)(16)(17), indicating that multiple regions have a role in modulating channel gating. For example, the combination of site-specific introduction of Cys residues and covalent modification by thiol-reactive reagents has shown that the pre-M2 region of ENaC subunits has a role in the regulation of channel gating (16,18,19).…”

mentioning

confidence: 99%

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Mutations in the Pore Region Modify Epithelial Sodium Channel Gating by Shear Stress

Carattino

Sheng

Kleyman

2005

Journal of Biological Chemistry

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Previous studies have shown that epithelial Na؉ channels (ENaCs) are activated by laminar shear stress (LSS). ENaCs with a high intrinsic open probability because of a mutation (␤S518K) or covalent modification of an introduced Cys residue (␣S580C) in the pre-second transmembrane domain (pre-M2) were not activated by LSS, suggesting that the pre-M2 region participates in conformational rearrangements during channel activation. We examined the role of the pore region of the ␣-subunit in channel gating by studying the kinetics of activation by LSS of wild- ) resulted in a reduction in the LSS response, and exhibited a multiexponential time course of activation. The corresponding ␥-subunit mutant (␣␤␥G542C) had a minimal response to LSS and exhibited a high intrinsic open probability. These data suggest that residues in the pore region participate in the sensing and/or transduction of the mechanical stimulus that results in channel activation and are consistent with the hypothesis that the ENaC pore region has a key role in modulating channel gating.The amiloride-sensitive epithelial sodium channel (ENaC)

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Regulation of Transport in the Connecting Tubule and Cortical Collecting Duct

Staruschenko

2012

Comprehensive Physiology

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The central goal of this overview article is to summarize recent findings in renal epithelial transport, focusing chiefly on the connecting tubule (CNT) and the cortical collecting duct (CCD). Mammalian CCD and CNT are involved in fine tuning of electrolyte and fluid balance through reabsorption and secretion. Specific transporters and channels mediate vectorial movements of water and solutes in these segments. Although only a small percent of the glomerular filtrate reaches the CNT and CCD, these segments are critical for water and electrolyte homeostasis since several hormones, e.g. aldosterone and arginine vasopressin, exert their main effects in these nephron sites. Importantly, hormones regulate the function of the entire nephron and kidney by affecting channels and transporters in the CNT and CCD. Knowledge about the physiological and pathophysiological regulation of transport in the CNT and CCD and particular roles of specific channels/transporters has increased tremendously over the last two decades. Recent studies shed new light on several key questions concerning the regulation of renal transport. Precise distribution patterns of transport proteins in the CCD and CNT will be reviewed, and their physiological roles and mechanisms mediating ion transport in these segments will be also covered. Special emphasis will be given to pathophysiological conditions appearing as a result of abnormalities in renal transport in the CNT and CCD.

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Epithelial Na+ Channels Are Activated by Laminar Shear Stress

Cited by 143 publications

References 35 publications

Distinct Apical and Basolateral Membrane Requirements for Stretch-induced Membrane Traffic at the Apical Surface of Bladder Umbrella Cells

Distinct Apical and Basolateral Membrane Requirements for Stretch-induced Membrane Traffic at the Apical Surface of Bladder Umbrella Cells

Mutations in the Pore Region Modify Epithelial Sodium Channel Gating by Shear Stress

Regulation of Transport in the Connecting Tubule and Cortical Collecting Duct

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