Epithelial sodium channels: function, structure, and regulation

Garty, Haim; Palmer, Lawrence G.

doi:10.1152/physrev.1997.77.2.359

Cited by 1,078 publications

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“…This current was completely inhibited by amiloride (Fig. 3A), a blocker of ENaC (30,31). Stimulation by cold temperature was not dependent on voltage; a temperature of 10°C increased Na ϩ current at all voltages tested (Ϫ120 to ϩ40 mV, Fig.…”

Section: Resultsmentioning

confidence: 87%

DEG/ENaC ion channels involved in sensory transduction are modulated by cold temperature

Askwith

Benson

Welsh

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

155

102

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Several DEG͞ENaC cation channel subunits are expressed in the tongue and in cutaneous sensory neurons, where they are postulated to function as receptors for salt and sour taste and for touch. Because these tissues are exposed to large temperature variations, we examined how temperature affects DEG͞ENaC channel function. We found that cold temperature markedly increased the constitutively active Na ؉ currents generated by epithelial Na ؉ channels (ENaC). Half-maximal stimulation occurred at 25°C. Cold temperature did not induce current from other DEG͞ENaC family members (BNC1, ASIC, and DRASIC). However, when these channels were activated by acid, cold temperature potentiated the currents by slowing the rate of desensitization. Potentiation was abolished by a ''Deg'' mutation that alters channel gating. Temperature changes in the physiologic range had prominent effects on current in cells heterologously expressing acid-gated DEG͞ENaC channels, as well as in dorsal root ganglion sensory neurons. The finding that cold temperature modulates DEG͞ENaC channel function may provide a molecular explanation for the widely recognized ability of temperature to modify taste sensation and mechanosensation.T emperature is known to modulate sensations such as taste and touch. For example, personal experience informs us that temperature is key to the taste of food and wine. The interplay between temperature and sensory perception may occur by many mechanisms, including the direct action of temperature on sensory receptors.Recent studies have suggested that several members of the DEG͞ENaC family of cation channels may function as sensory receptors (for reviews see refs. 1 and 2). In Caenorhabditis elegans, the DEG͞ENaC channel subunits MEC-4 and MEC-10 are expressed in touch cell neurons, where they are thought to form part of the mechanoreceptor complex (3). In mammals, the DEG͞ENaC channel BNC1 (4) [also called MDEG (5), BNaC1 (6), and ASIC2 (2)] is expressed in lanceolate nerve endings at the site of mechanotransduction (7). Targeted disruption of the BNC1 gene in mice reduced the sensitivity of low-threshold, rapidly adapting mechanoreceptors, indicating that BNC1 is required for normal touch sensation (7). The related channel subunits ASIC (8) [also called BNaC2 (6) and ASIC1 (2)] and DRASIC (9) [also called ASIC3 (2)] are also expressed in peripheral sensory neurons; because they are activated by acidic pH, it has been proposed that they play a role in nociception (2). The mammalian epithelial Na ϩ channel (ENaC) subunits may also function in touch sensation; ␤-and ␥ENaC are expressed in Merkel cell͞neurite complexes, in lamellated corpuscles of the rat foot pad, and in lanceolate nerve endings of the vibrissal follicle (10, 11). BNC1 and all three ENaC subunits (␣, ␤, ␥) are also expressed in the tongue. On the basis of their localization in the apical membrane of taste receptor cells, DEG͞ENaC subunits may be receptors for salt taste (ENaC) (12-14) and sour taste (BNC1) (15). Consistent with these hypotheses, salt taste ...

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Section: Resultsmentioning

confidence: 87%

DEG/ENaC ion channels involved in sensory transduction are modulated by cold temperature

Askwith

Benson

Welsh

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

155

102

View full text Add to dashboard Cite

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“…touch, pain and thermoregulation) (Oláh et al, 2012). For example, ENaC, an epithelial sodium channel with a key role in regulating the transport of sodium ions in electrically tight epithelia such as the renal collecting duct (Garty and Palmer, 1997), is also expressed in the epidermis and cultured keratinocytes (Brouard et al, 1999), and appears to be required for the directional migration of keratinocytes in an electric field, indicating a role for ENaC in wound healing (Yang et al, 2013). Utilising next-generation sequencing technologies, numerous new genes that are involved in inherited skin diseases are being identified.…”

Section: Perspectivesmentioning

confidence: 99%

Defective channels lead to an impaired skin barrier

Blaydon¹,

Kelsell²

2014

Journal of Cell Science

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Channels are integral membrane proteins that form a pore, allowing the passive movement of ions or molecules across a membrane (along a gradient), either between compartments within a cell, between intracellular and extracellular environments or between adjacent cells. The ability of cells to communicate with one another and with their environment is a crucial part of the normal physiology of a tissue that allows it to carry out its function. Cell communication is particularly important during keratinocyte differentiation and formation of the skin barrier. Keratinocytes in the skin epidermis undergo a programme of apoptosis-driven terminal differentiation, whereby proliferating keratinocytes in the basal (deepest) layer of the epidermis stop proliferating, exit the basal layer and move up through the spinous and granular layers of the epidermis to form the stratum corneum, the external barrier. Genes encoding different families of channel proteins have been found to harbour mutations linked to a variety of rare inherited monogenic skin diseases. In this Commentary, we discuss how human genetic findings in aquaporin (AQP) and transient receptor potential (TRP) channels reveal different mechanisms by which these channel proteins function to ensure the proper formation and maintenance of the skin barrier.

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“…The epithelial Na + channel (ENaC) located in the distal nephrons of the kidney, and in the lung, sweat glands and colon is an essential component of the body's salt-and-water-regulation system [1]. The Na + channel is composed of three subunits called α, β and γ that share similar primary sequences [2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, Staub et al [23] reported that the WW domains of the ubiquitin-protein ligase Nedd4 [neuronal precursor cell expressed developmentally downregulated (gene 4)] bind to the PPPXY (PY) motifs found in the C-terminus of all three subunits, and that the α and γ subunits Abbreviations used : ENaC, epithelial Na + channel ; hENaC, human ENaC ; αhENaC, α subunit of hENaC ; GST, glutathione S-transferase ; SH3, Src homology 3 ; PY motif, PPPXY motif ; MDCK, Madin-Darby canine kidney ; HA, haemagglutinin ; hNedd4, human Nedd4 ; WWP, WW-domain-containing protein. 1 To whom correspondence should be addressed (e-mail fiona.mcdonald!vuw.ac.nz).…”

Section: Introductionmentioning

confidence: 99%