Tissue acidosis (decrease in pH below the physiological level) that occurs in ischemia, tissue damage or inflammation is accompanied by pain. Acidosis is also observed in muscle during exercise or in experimental cardiac infarction. Perception of low extracellular pH is relayed to the brain by the initiation of multiphasic inward currents in both CNS and peripheral sensory neurons, DRG (dorsal root ganglion neurons). At the molecular level, H+-gated cation channels are activated by low pH in nociceptive neurons. Recent cloning and characterization of H+-gated cation channels suggest that they are members of the NaC/DEG superfamily of sodium channels that include: (1) Amiloride-sensitive epithelial Na+ channel proteins (alpha, beta, and gamma, and delta-ENaC subunits) expressed in epithelia of the vertebrate kidney, colon, lung, tongue, and brain. The ENaC subunits may form heterotrimeric active Na channel. ENaCs are involved in Na and water readsorption, and salty taste transduction) of vertebrate colon, lung, kidney and tongue. (2) A molluscan cardioexcitatory peptide FMRFamide-gated channel (FaNaC), (3) and mechanosensory channel proteins of nematode degenerins (DEG). At least 17 proteins and numerous ortholog have been identified in the superfamily of DEG/NaC are characterized by intracellular N and C-termini, two transmembrane domains, and a large extracellular loop with several conserved cysteines. All members of this family are selective for Na+ and blocked by amiloride.

ENaC-alpha subunits have been cloned from various tissues and from several species (human 669 aa, rat 698 aa, mouse 699 aa; ~80% inter-species homology). It mediates electrodiffusion of the luminal Na (and water which follows osmotically) through the apical membrane of epithelial cells. It also controls the reabsorption of Na in kidney, colon, lung, and sweat glands. ENaC-a has also been implicated in taste perception. Defects in ENaC-a are one of the cause of pseudohypoaldosteronism type I, a rare salt wasting disease characterized by dehydration, hyponatacemia, hyperkalemia, and acidosis. Inactivation of ENaC-a in transgenic mice causes an early death due to defective lung liquid clearance.

ENaC-beta subunit (mouse/rat 638 aa, human 640 aa), ENaC-gamma subunit (mouse 655 aa, rat 650 aa, and human 649 aa) are expressed in lung, kidney, colon and other tissues. ENaC-b from various species are ~80% identical, and only ~30% similarity with the ENaC-a ENaC-delta (human 638 aa) is expressed mainly in brain, pancreas, testis, and ovary. It is 27-30% homologous with the other ENaCs. It can associate with b, and g ENaC to form a functional channel.

ADI has produced highly specific rabbit antibodies for various ENaCs using antigenic peptide sequences unique to each protein. These antibodies do not crossreact with each other and can be used to study various ENaCs. Respective antigenic or control peptides are also available to confirm specificity of antibodies.
 

m=mouse; r=rat; h=human; c=chicken; f=frog; ~CT or ~NT=near C or N-terminus. Control peptides are actual peptides used for immunization. Because of their small size (1.5-2K) they are not suitable for Western. They should be used for ELISA or for antibody blocking studies.

"Neat Antisera" are the unpurified antiserum and it is suitable for ELISA and Western.
"Affinity pure" antibodies have been over the antigen-affinity column and recommended for immunohistochemical applications.
"Control peptides" can not be used for Western as they are very short peptides. They are intended for ELISA or antibody competition studies.