Disease relevance of Scnn1g

• Liddle's syndrome, an inherited form of hypertension, is caused by mutations that delete or alter PY domains in the carboxyl termini of beta or gamma ENaC subunits, leading to increased channel activity [1].

High impact information on Scnn1g

• The ENaC is a multimeric protein composed of alpha-ENaC, beta-ENaC, and gamma-ENaC subunits [2].
• By two-electrode voltage clamp recordings, we demonstrated that PIP(2) and PIP(3) significantly increased amiloride-sensitive current in Xenopus oocytes injected with cRNAs of rat alpha-, beta-, and gamma-ENaC [3].
• The cytosolic termini of the beta- and gamma-ENaC subunits are involved in the functional interactions between cystic fibrosis transmembrane conductance regulator and epithelial sodium channel [4].
• The gamma-ENaC underwent a complex change associated with increased abundance of the 70-kD band with a concomitant decrease in the main 85-kD band, corresponding to an aldosterone effect [5].
• Overall, the increase in aldosterone observed in vasopressin escape is not necessary for the increased expression of NCC, alpha- or gamma-ENaC or increased MAP associated with "escape."[6]

Biological context of Scnn1g

• These results identify a marked and highly segment-specific downregulation of beta-ENaC and gamma-ENaC in the cortical and outer medullary collecting duct, chief sites for collecting duct sodium reabsorption, in rats with a lithium-induced increase in fractional excretion of sodium [7].
• Time correlation of beta- and gamma-ENaC induction and J(Na) stimulation suggests that the early aldosterone effect on Na(+) absorption in distal colon is caused by transcriptional upregulation of beta- and gamma-ENaC expression [8].
• The gene for the gamma-ENAC was located on rat chromosome 1 [9].
• Our results identify the N-terminus of the alpha-subunit as a major determinant of kinetic behavior of both homooligomeric and heterooligomeric ENaCs, although the carboxy-terminal domains of beta- and gamma-ENaC subunits play important role(s) in modulation of the kinetics of heterooligomeric channels [10].

Anatomical context of Scnn1g

• Immunoperoxidase brightfield- and laser-scanning confocal fluorescence microscopy demonstrated increased targeting of alpha-ENaC, beta-ENaC, and gamma-ENaC subunits to the apical plasma membrane in the distal convoluted tubule (DCT2), connecting tubule, and cortical and medullary collecting duct segments [11].
• The purpose of the present study was to investigate the cellular localization of ENaC subunits in the rat inner ear immunohistochemically with the specific polyclonal rabbit antibodies against the rat alpha-, beta- and gamma-ENaC [12].
• Mutants of the PY motif in beta- and gamma-ENaC subunits (beta-Y618A, beta-P616L, beta-R564stop, and gamma-K570stop) were stably expressed by retroviral gene transfer in a renal cortical collecting duct cell line (mpkCCDcl4), and transepithelial Na+ transport was assessed by measurements of the benzamil-sensitive short-circuit current (Isc) [13].
• Tyrosine kinase A (TrkA) receptor blockade abolished NGF-induced beta- and gamma-ENaC expression and neurite formation [14].
• Western-blot analysis and RT-PCR techniques, however, revealed that alpha-, beta-, as well as gamma-ENaC are, in fact, expressed in rat hepatocytes [15].

Associations of Scnn1g with chemical compounds

• Immunoblotting revealed that lithium treatment induced a marked decrease in the protein abundance of beta-ENaC and gamma-ENaC in the cortex and outer medulla [7].
• Whole kidney abundance of AQP3, the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), and gamma-ENaC (85-kDa band) correlated most strongly with blood glucose in study 3 [16].
• However, after a 1-day lag, plasma aldosterone levels increased in association with increases in abundances of three aldosterone-regulated Na transporter proteins: the thiazide-sensitive Na-Cl cotransporter (NCC), the alpha-subunit of the amiloride-sensitive epithelial Na channel (alpha-ENaC), and the 70-kDa form of gamma-ENaC [17].

Analytical, diagnostic and therapeutic context of Scnn1g

• Moreover, immunohistochemistry and laser confocal microscopy demonstrated an almost complete absence of beta-ENaC and gamma-ENaC labeling in cortical and outer medullary collecting duct, which was not affected by dietary sodium intake [7].
• Here we show by real-time RT-PCR and immunofluorescence that an aldosterone injection in adrenalectomized rats induces alpha-ENaC subunit expression along the entire ASDN within 2 h, whereas beta- and gamma-ENaC are constitutively expressed [18].
• Using immunocytochemistry, we found that alpha-, beta-, and gamma-ENaC subunits and stomatin are localized in the perikarya of the trigeminal neurons and in a minor fraction of their termination site in the vibrissal follicle-sinus complex, where longitudinal lanceolate endings are immunopositive [19].

References