scholarly journals Membrane trafficking pathways regulating the epithelial Na+ channel

2020 ◽  
Vol 318 (1) ◽  
pp. F1-F13 ◽  
Author(s):  
Adam W. Ware ◽  
Sahib R. Rasulov ◽  
Tanya T. Cheung ◽  
J. Shaun Lott ◽  
Fiona J McDonald
Keyword(s):  
Cell Surface ◽  
Blood Volume ◽  
Membrane Trafficking ◽  
Apical Membrane ◽  
Na Channel ◽  
Membrane Domain ◽  
Multiple Forms ◽  
Epithelial Na Channel

Renal Na+ reabsorption, facilitated by the epithelial Na+ channel (ENaC), is subject to multiple forms of control to ensure optimal body blood volume and pressure through altering both the ENaC population and activity at the cell surface. Here, the focus is on regulating the number of ENaCs present in the apical membrane domain through pathways of ENaC synthesis and targeting to the apical membrane as well as ENaC removal, recycling, and degradation. Finally, the mechanisms by which ENaC trafficking pathways are regulated are summarized.

scholarly journals Specific and Nonspecific Effects of Protein Kinase C on the Epithelial Na + Channel

2000 ◽  
Vol 115 (5) ◽  
pp. 559-570 ◽  
Author(s):  
Mouhamed S. Awayda
Keyword(s):  
Membrane Trafficking ◽  
Expression System ◽  
Na Channel ◽  
Specific Effects ◽  
Nonspecific Effects ◽  
Oocyte Expression ◽  
Xenopus Oocyte Expression ◽  
Oocyte Expression System ◽  
Baseline Values ◽  
Epithelial Na Channel

The Xenopus oocyte expression system was used to explore the mechanisms of inhibition of the cloned rat epithelial Na+ channel (rENaC) by PKC (Awayda, M.S., I.I. Ismailov, B.K. Berdiev, C.M. Fuller, and D.J. Benos. 1996. J. Gen. Physiol. 108:49–65) and to determine whether human ENaC exhibits similar regulation. Effects of PKC activation on membrane and/or channel trafficking were determined using impedance analysis as an indirect measure of membrane area. hENaC-expressing oocytes exhibited an appreciable activation by hyperpolarizing voltages. This activation could be fit with a single exponential, described by a time constant (τ) and a magnitude (ΔI V). A similar but smaller magnitude of activation was also observed in oocytes expressing rENaC. This activation likely corresponds to the previously described effect of hyperpolarizing voltage on gating of the native Na+ channel (Palmer, L.G., and G. Frindt. 1996. J. Gen. Physiol. 107:35–45). Stimulation of PKC with 100 nM PMA decreased ΔIV in hENaC-expressing oocytes to a plateau at 57.1 ± 4.9% (n = 6) of baseline values at 20 min. Similar effects were observed in rENaC-expressing oocytes. PMA decreased the amiloride-sensitive hENaC slope conductance (gNa) to 21.7 ± 7.2% (n = 6) of baseline values at 30 min. This decrease was similar to that previously reported for rENaC. This decrease of g Na was attributed to a decrease of membrane capacitance (C m), as well as the specific conductance (gm/Cm ). The effects on gm/Cm reached a plateau within 15 min, at ∼60% of baseline values. This decrease is likely due to the specific ability of PKC to inhibit ENaC. On the other hand, the decrease of Cm was unrelated to ENaC and is likely an effect of PKC on membrane trafficking, as it was observed in ENaC-expressing as well as control oocytes. At lower PMA concentrations (0.5 nM), smaller changes of Cm were observed in rENaC- and hENaC-expressing oocytes, and were preceded by larger changes of gm and by changes of gm/Cm, indicating specific effects on ENaC. These findings indicate that PKC exhibits multiple and specific effects on ENaC, as well as nonspecific effects on membrane trafficking. Moreover, these findings provide the electrophysiological basis for assessing channel-specific effects of PKC in the Xenopus oocyte expression system.

scholarly journals FoxO1 inhibits transcription and membrane trafficking of epithelial Na+ channel

2015 ◽  
Vol 128 (19) ◽  
pp. 3621-3630 ◽  
Author(s):  
Y. Shen ◽  
W. Xu ◽  
H. You ◽  
D. Su ◽  
J. Xing ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Na Channel ◽  
Epithelial Na Channel

scholarly journals An SH3 binding region in the epithelial Na+ channel (alpha rENaC) mediates its localization at the apical membrane.

1994 ◽  
Vol 13 (19) ◽  
pp. 4440-4450 ◽  
Author(s):  
D. Rotin ◽  
D. Bar-Sagi ◽  
H. O'Brodovich ◽  
J. Merilainen ◽  
V.P. Lehto ◽  
...  
Keyword(s):  
Apical Membrane ◽  
Na Channel ◽  
Binding Region ◽  
Epithelial Na Channel

scholarly journals Interactive Actions of Aldosterone and Insulin on Epithelial Na+ Channel Trafficking

2020 ◽  
Vol 21 (10) ◽  
pp. 3407 ◽  
Author(s):  
Rie Marunaka ◽  
Yoshinori Marunaka
Keyword(s):  
Blood Pressure ◽  
Inhibitory Action ◽  
Apical Membrane ◽  
Short Circuit ◽  
Recycling Rate ◽  
Na Channel ◽  
Stimulatory Action ◽  
Channel Trafficking ◽  
Short Circuit Currents ◽  
Epithelial Na Channel

Epithelial Na+ channel (ENaC) participates in renal epithelial Na+ reabsorption, controlling blood pressure. Aldosterone and insulin elevate blood pressure by increasing the ENaC-mediated Na+ reabsorption. However, little information is available on the interactive action of aldosterone and insulin on the ENaC-mediated Na+ reabsorption. In the present study, we tried to clarify if insulin would modify the aldosterone action on the ENaC-mediated Na+ reabsorption from a viewpoint of intracellular ENaC trafficking. We measured the ENaC-mediated Na+ transport as short-circuit currents using a four-state mathematical ENaC trafficking model in renal A6 epithelial cells with or without aldosterone treatment under the insulin-stimulated and -unstimulated conditions. We found that: (A) under the insulin-stimulated condition, aldosterone treatment (1 µM for 20 h) significantly elevated the ENaC insertion rate to the apical membrane ( k I ) 3.3-fold and the ENaC recycling rate ( k R ) 2.0-fold, but diminished the ENaC degradation rate ( k D ) 0.7-fold without any significant effect on the ENaC endocytotic rate ( k E ); (B) under the insulin-unstimulated condition, aldosterone treatment decreased k E 0.5-fold and increased k R 1.4-fold, without any significant effect on k I or k D . Thus, the present study indicates that: (1) insulin masks the well-known inhibitory action of aldosterone on the ENaC endocytotic rate; (2) insulin induces a stimulatory action of aldosterone on ENaC apical insertion and an inhibitory action of aldosterone on ENaC degradation; (3) insulin enhances the aldosterone action on ENaC recycling; (4) insulin has a more effective action on diminution of ENaC endocytosis than aldosterone.

scholarly journals Minireview: Regulation of Epithelial Na+ Channel Trafficking

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5079-5085 ◽  
Author(s):  
Peter M. Snyder
Keyword(s):  
Cell Surface ◽  
Collecting Duct ◽  
Distal Colon ◽  
Pressure Control ◽  
Na Channel ◽  
Na Transport ◽  
Channel Trafficking ◽  
C Terminus ◽  
Convergence Point ◽  
Epithelial Na Channel

The epithelial Na+ channel (ENaC) is a pathway for Na+ transport across epithelia, including the kidney collecting duct, lung, and distal colon. ENaC is critical for Na+ homeostasis and blood pressure control; defects in ENaC function and regulation are responsible for inherited forms of hypertension and hypotension and may contribute to the pathogenesis of cystic fibrosis and other lung diseases. An emerging theme is that epithelial Na+ transport is regulated in large part through trafficking mechanisms that control ENaC expression at the cell surface. ENaC trafficking is regulated at multiple steps. Delivery of channels to the cell surface is regulated by aldosterone (and corticosteroids) and vasopressin, which increase ENaC synthesis and exocytosis, respectively. Conversely, endocytosis and degradation is controlled by a sequence located in the C terminus of α, β, and γENaC (PPPXYXXL). This sequence functions as an endocytosis motif and as a binding site for Nedd4-2, an E3 ubiquitin protein ligase that targets ENaC for degradation. Mutations that delete or disrupt this motif cause accumulation of channels at the cell surface, resulting in Liddle’s syndrome, an inherited form of hypertension. Nedd4-2 is a central convergence point for ENaC regulation by aldosterone and vasopressin; both induce phosphorylation of a common set of three Nedd4-2 residues, which blocks Nedd4-2 binding to ENaC. Thus, aldosterone and vasopressin regulate epithelial Na+ transport in part by altering ENaC trafficking to and from the cell surface.

What Is New About the Structure of the Epithelial Na+ Channel ?

Physiology ◽  
1996 ◽  
Vol 11 (5) ◽  
pp. 195-201
Author(s):  
CM Canessa
Keyword(s):  
Ion Channels ◽  
Apical Membrane ◽  
Na Channel ◽  
Full Activity ◽  
New Family ◽  
Epithelial Na Channel ◽  
Tight Epithelium

The epithelial Na+ channel (ENaC) in the apical membrane of tight epithelium represents the first member of a new family of ion channels. The channel is formed by the association of three homologous subunits, a-, b-, and g-ENaC, that functionally complement to give full activity to the channel complex.

Single-channel behavior of a purified epithelial Na+ channel subunit that binds amiloride

1992 ◽  
Vol 263 (5) ◽  
pp. C1111-C1117 ◽  
Author(s):  
S. Sariban-Sohraby ◽  
M. Abramow ◽  
R. S. Fisher
Keyword(s):  
Single Channel ◽  
Apical Membrane ◽  
Na Channel ◽  
Na Transport ◽  
Patch Clamp Technique ◽  
Transport Inhibitor ◽  
Open Time ◽  
The Mean ◽  
Epithelial Na Channel ◽  
Binding Subunit

The apical membrane of high electrical resistance epithelia, which is selectively permeable to Na+, plays an essential role in the maintenance of salt balance. Na+ entry from the apical fluid into the cells is mediated by amiloride-blockable Na(+)-specific channels. The channel protein, purified from both amphibian and mammalian sources, is composed of several subunits, only one of which the 150-kDa polypeptide, specifically binds the Na+ transport inhibitor amiloride. The goal of the present study was to investigate whether the isolated amiloride-binding subunit of the channel could conduct Na+. The patch-clamp technique was used to study the 150-kDa polypeptide incorporated into a lipid bilayer formed on the tip of a glass pipette. Unitary conductance jumps averaged 4.8 pS at 100 mM Na2HPO4. Open times ranged from 24 ms to several seconds. The channel spent most of the time in the closed state. Channel conductance and gating were independent of voltage between -60 and +100 mV. Amiloride (0.1 microM) decreased the mean open time of the channel by 98%. We conclude that the 150-kDa subunit of the amiloride-blockable Na+ channel conducts current and may be sufficient for the Na+ transport function of the whole channel.

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