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.

Gap junctions in rabbit corneal epithelium: limited permeability and inhibition by cAMP

1991 ◽  
Vol 261 (5) ◽  
pp. C857-C864 ◽  
Author(s):  
J. M. Wolosin
Keyword(s):  
Gap Junctions ◽  
Apical Membrane ◽  
Short Circuit ◽  
Basolateral Membrane ◽  
Ringer Solution ◽  
Camp Concentration ◽  
Ussing Chambers ◽  
Side Channels ◽  
Short Circuit Currents ◽  
Camp Elevation

Rabbit corneas were mounted in Ussing chambers, and the apical membrane of the superficial cells (SCs) was permeabilized by exposure to digitonin in a Ca(2+)-free Ringer solution. This treatment resulted in the generation of large (60.7 +/- 13.2 microA/cm2, n = 25) Na(+)-dependent tear (T)-to-stroma (S) short-circuit currents (Isc). The Isc was abolished by ouabain and by 1.4 mM Ca2+ and was inhibited by heptanol, 18 alpha-glycyrrhetinic acid, and dieldrin, effects consistent with the notion that corneal transepithelial fluxes include translocations through gap junctions (GJs) before basolateral membrane transport. T-to-S Isc were also generated when T-side Na+ was replaced by K+, eliciting a T-to-S K+ flux via basolateral K+ channels and when, with either Na+ or K+ on the T side, channels were introduced at the apical membrane with amphotericin B. The Isc in all four conditions exhibited similar sensitivity to GJ inhibitors and were inhibited by adenosine 3',5'-cyclic monophosphate (cAMP) elevation. Fluorophotometry combined with SC permeabilization with digitonin demonstrated that the half-time for the SC to sub-SC movement of 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (mol wt 540) exceeded 3 h. These results indicate that junctional communications along the epithelial stratification axis are highly restricted and modulated by cAMP concentration.

Apical nonspecific cation conductances in rabbit cecum

1994 ◽  
Vol 266 (3) ◽  
pp. G475-G484 ◽  
Author(s):  
J. H. Sellin ◽  
W. P. Dubinsky
Keyword(s):  
Epithelial Transport ◽  
Apical Membrane ◽  
Divalent Cations ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Na Channel ◽  
Similar Response ◽  
Electrogenic Transport

Rabbit cecum exhibits electrogenic Na absorption in vitro. However, because this transport process is not inhibited by amiloride nor does it demonstrate saturation kinetics typical of the amiloride-inhibitable Na channel, we considered whether the cecal transporter represented one of a recently described family of nonselective cation conductances or channels (NSCC). Both transepithelial and vesicle studies demonstrated that K, Cs, and Rb were transported via an apical conductance. Electrogenic transport was inhibited by divalent cations including Ca, Mg, and Ba but was unaffected by either lanthanum or gadolinium. Parallel studies in distal colon did not exhibit a similar response to either K substitution or Ba inhibition. Phenamil, verapamil, and nicardipine significantly inhibited the short-circuit current (Isc). stimulated by nominal Ca- and Mg-free conditions. Flux studies demonstrated a correlation between changes in Isc and Na transport. Microelectrode impalement studies suggested that there may be both NSCC and K conductance in the apical membrane. Planar bilayer studies identified a 190-pS cation channel that may correlate with the macroscopic transport properties of this epithelium. These studies are consistent with a model of cecal Na absorption mediated by a NSCC in the apical membrane; this may be the mechanism underlying the distinct epithelial transport characteristics of this intestinal segment.

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

The Epithelial Na+ Channel as a Determinant of Blood Pressure

2007 ◽  
Vol 3 (1) ◽  
pp. 45-49 ◽  
Author(s):  
Timothy Burton ◽  
Kevin O'Shaughnessy ◽  
Morris Brown
Keyword(s):  
Blood Pressure ◽  
Na Channel ◽  
Epithelial Na Channel

Electrophysiology and noise analysis of K+-depolarized epithelia of frog skin

1985 ◽  
Vol 249 (5) ◽  
pp. C421-C429 ◽  
Author(s):  
J. Tang ◽  
F. J. Abramcheck ◽  
W. Van Driessche ◽  
S. I. Helman
Keyword(s):  
Frog Skin ◽  
Single Channel ◽  
Apical Membrane ◽  
Short Circuit ◽  
Noise Analysis ◽  
Basolateral Membrane ◽  
Short Circuit Current ◽  
Membrane Resistance ◽  
Na Channel ◽  
Channel Density

Epithelia of frog skin bathed either symmetrically with a sulfate-Ringer solution or bathed asymmetrically and depolarized with a 112 mM K+ basolateral solution (Kb+) were studied with intracellular microelectrode techniques. Kb+ depolarization caused an initial decrease of the short-circuit current (Isc) with a subsequent return of the Isc toward control values in 60-90 min. Whereas basolateral membrane resistance (Rb) and voltage were decreased markedly by high [Kb+], apical membrane electrical resistance (Ra) was decreased also. After 60 min, intracellular voltage averaged -27.3 mV, transcellular fractional resistance (fRa) was 86.8%, and Ra and Rb were decreased to 36.1 and 13.0%, of their control values, respectively. Amiloride-induced noise analysis of the apical membrane Na+ channels revealed that Na+ channel density was increased approximately 72% while single-channel Na+ current was decreased to 39.9% of control, roughly proportional to the decrease of apical membrane voltage (34.0% of control). In control and Kb+-depolarized epithelia, the Na+ channel density exhibited a phenomenon of autoregulation. Inhibition of Na+ entry (by amiloride) caused large increases of Na+ channel density toward saturating values of approximately 520 X 10(6) channels/cm2 in Kb+-depolarized tissues.

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.

scholarly journals Contribution of Renal Epithelial Na Channel (ENaC) in Clofibrate‐mediated Reduction in Blood Pressure in Female SHR

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
Zivar Yousefipour ◽  
Robyn Butler ◽  
Mohammad Newaz ◽  
Adebayo Oyekan
Keyword(s):  
Blood Pressure ◽  
Na Channel ◽  
Mediated Reduction ◽  
Epithelial Na Channel

Guanosine nucleotide-dependent activation of the amiloride-blockable Na+ channel

1989 ◽  
Vol 256 (5) ◽  
pp. F965-F969
Author(s):  
H. Garty ◽  
O. Yeger ◽  
A. Yanovsky ◽  
C. Asher
Keyword(s):  
Membrane Vesicles ◽  
Na Channel ◽  
Bladder Epithelium ◽  
Stimulatory Action ◽  
Fourfold Increase ◽  
Cyclic Monophosphate ◽  
Sustained Effect ◽  
22Na Uptake ◽  
Gamma S ◽  
Epithelial Na Channel

Effects of guanosine nucleotides on the epithelial Na+ channel were studied in apical membrane vesicles derived from the toad bladder epithelium. Trapping 10 microM guanosine-5'-O-(thiotriphosphate) (GTP gamma S) in vesicles evoked two- to fourfold increase in the amiloride-sensitive (Na+ channel-mediated) 22Na+ uptake. The nucleotide had no significant effect on the amiloride-insensitive 22Na+ uptake or the valinomycin-mediated 86Rb+ uptake in the same membranes. The stimulatory action of GTP gamma S was mimicked by 5'-guanylylimidiodiphosphate (GppNHp) and could at least partly be reversed by guanosine-5'-O-(thiodiphosphate) (GDP beta S) (10-fold excess). GTP itself and adenosine-5'-O-(thiotriphosphate) (ATP gamma S) had no sustained effect on Na+ transport in vesicles. Thus it appears that the epithelial Na+ channel is directly or indirectly regulated by the occupancy of a guanosine-specific site, probably the alpha subunit of a G protein. The possibility that GTP gamma S acts indirectly by activating a membrane-bound, GTP-dependent enzyme the product of which modulates the channel conductance was assessed by measuring 22Na+ fluxes in membrane vesicles prepared to contain products of such enzymes. None of the reagents tested [adenosine 3',5' cyclic monophosphate (cAMP), guanosine 3',5y cyclic monophosphate (cGMP), inositol 1,4,5-trisphosphate (IP3), and diacylglycerol (DAG)] increased the tracer flux in vesicles or altered its response to GTP gamma S.

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