Amiloride-sensitive Na+ Channel

The amiloride-sensitive Na+ channel (ENaC) is a cell membrane glycoprotein selective for sodium ions, which is composed of three subunits (a, (3 and y). Gating of sodium is inhibited by the diuretic amiloride. 

Amiloride-sensitive Na+ Channel y-Aminobutyric Acid (GABA) Aminoglycosides Aminopeptidase AMP, Cyclic... 

Amiloride-sensitive Na+ channels are probably absent from the pigmented rabbit conjunctival epithelium, since the conjunctival Ix is not sensitive to either mucosal or serosal amiloride up to 1 mM. Conjunctival Ix is, however, inhibited... 

Gilbertson, T. A. et al. Proton currents through amiloride-sensitive Na channels in hamster taste cells. Role in acid transduction./. Gen. Physiol. 100 803-824,1992. 

C. Ruckes, U. Blank, K. Moller, J. Rieboldt, H. Lindemann, G. Munker, W. Clauss, and W. M. Weber. Amiloride-sensitive Na+ channels in human nasal epithelium are different from classical epithelial Na+ channels. Biochem Biophys Res Commun 237 488-491 (1997). 

Sour taste is perceived via the effect of lowered pH on amiloride-sensitive Na+ channels and on the conductance properties of other PM-located ion channels (such as K+ channels). A variety of plant carboxylic acids contribute to a sour taste, the most familiar of these being acetic acid (as in vinegar) (Table 10.3). 

Gilbertson TA, Roper SD, ICinnamon SC. 1993. Proton currents through amiloride-sensitive Na channels in isolated hamster taste cells Enhancement by vasopressin and cAMP. Neuron 10 931-942. 

An amiloride-sensitive Na channel comprises four subunits that may be either identical or distinct but in any case are homologous. An individual subunit ranges in length from 500 to 1000 amino acids and includes two... 

Like taste, touch is a combination of sensory systems that are expressed in a common organ—in this case, the skin. The detection of pressure and the detection of temperature are two key components. Amiloride-sensitive Na channels, homologous to those of taste, appear to play a role. Other systems are responsible for detecting painful stimuli such as high temperature, acid, or certain specific chemicals. Although our understanding of this sensory system is not as advanced as that of the other sensory systems, recent work has revealed a fascinating relation between pain and taste sensation, a relation well known to anyone who has eaten spicy food. 

Molecular cloning studies recently have revealed that the amiloride-sensitive Na+ channel consists of three subunits (alpha, beta, gamma). Although the alpha subunit is sufficient for channel activity, maximal Na+ permeabihty is induced when all three subunits are coexpressed in the same cell, suggesting a minimal oligomeric structure in which one copy of each subunit is associated in a heterotrimeric protein. 

Salty tastants act directly on Na+ channels in the PM of cells on the tongue surface. Direct passage of Na+ through these channels causes depolarization and thence signalling to the CNS. Much (but not all) salt taste perception is inhibited by the voltage-sensitive Na+ channel inhibitor amiloride (see Chapter 4) and evidently some salt perception also occurs via amiloride-insensitive channels. 

Ciampolillo, F, McCoy, D., Green, R. B., Karlson, K. FI., Dagenais, A., Molday, R. S., and Stanton, B. A. (1996). Cell-specific expression of amiloride-sensitive Na+-conducting ion channels in the kidney. Am. J. Physiol. 271, C1303-C1315. 

Salty tastants are not detected by 7TM receptors. Rather, they are detected directly by their passage through ion channels expressed on the surface of cells in the tongue. Evidence for the role of these ion channels comes from examining known properties of Na channels characterized in other biological contexts. One class of channels, characterized first for their role in salt reabsorption, are thought to be important in the detection of salty tastes because they are sensitive to the compound amiloride, which mutes the taste of salt and significantly lowers sensory-neuron activation in response to sodium. 

The steroid hormone aldosterone, synthesized in the zona glomerulosa of the adrenal cortex, also plays an important role in maintaining blood osmolar-ity. It binds its receptors in the cytoplasm of epithelial cells of the distal colon and the renal nephron, followed by translocation of the hormone-receptor complex to the nucleus and activation of transolption of ion transport genes to increase Na reabsorption and secretion. Water follows Na+ movement by osmosis. These transporters include the luminal amiloride-sensitive epilheUal Na+ channel, the luminal channel, the serosal Na, K+-ATPase, the Na+/H+exchanger, and the NaVCT cotransporter. 

A special class of epithelial Na channels (ENaC), located in the apical epithelial membranes, mediate the active Na" " reabsorption in kidney, colon, lung, and sweat glands they are essential for the maintenance of the body s salt and water balance. The ENaC are completely different from the Nay channels and are not sensitive to TTX. Instead, they are inhibited with high affinity by amiloride, which is an established diuretic drug. ENaC form four channel subfamilies a, (3, y, and 5. Structurally they are 510 to 920 amino acid proteins with two TM segments separated by a large extracellular loop and have a single channel conductance of 4 to 5 pA. 

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