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, gamma, and delta ENaC subunits) are 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). The DEG genes of the nematode C. elegans show a rare gain of function mutations causing swelling, vacuolation, and eventual cell death. At least 17 proteins and numerous ortholog have been identified in the superfamily of DEG/NaC that 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.

The mammalian neuronal homolog of degenerins (MDEG or MDEG1; now designated ASIC2; rat/human 512 aa) is identical with brain type Na channel (BNAC1 or BNC1). The other isoform of BnaC1, BNaC2 is also exclusively expressed in brain. MDEG1/ASIC2 shares 67% identity with ASIC (Acid Sensing Ion Channel or now called ASIC1). Rat ASIC1 (rat 526 aa, human 528/574 aa) shares 92% homology with human BNaC2 and may be the rat ortholog of human BNaC2. ASIC1, expressed in brain and dorsal root ganglions (DRG) cells, is activated by pH <7.0. MDEG1 requires more acidic pH than ASIC1 and has slower activation kinetic.

A splice variant of rat ASIC, termed ASIC-b (rat 513 aa), which contains a unique 172-aa n-terminal domain, is expressed only in a subset of small and large diameter sensory neurons and absent in sympathetic neurons and CNS. Unlike ASIC, ASIC-b is not permeable to calcium. It forms a functional channel with electrophysiological properties different from ASIC and DRASIC.

MDEG2 (now designated ASIC2b; rat/mouse 563 aa), a splice variant of MDEG1, differs in the first 236 aa, is expressed in both brain and sensory neurons. MDEG2 is activated neither by mutations nor low pH. However, it acts as modulatory subunit when associated with MDEG1 and another H+-activated channel, DRASIC (Dorsal Root ganglion ASIC now designated ASIC3). DRASIC (rat 533 aa, human 531 aa) is specific for sensory neurons. In response to a drop in pH, DRASIC gives rise to a biphasic currents with poor discrimination between Na+ and K+. This sustained current may be important in pain sensation due to acidosis. Recently, a DRASIC homolog, hTNaC1 (human testis Na Channel 1; 532 aa; 82% homology with DRASIC) has been cloned that is specific for testes.

More recently, a new member of ASIC family, termed ASIC4, has been cloned and characterized from rat and human. ASIC4/SPASIC (human 539/666 aa, chromosome 2; rat 539 aa, ~97% homology between rat and human) is strongly expressed in pituitary and also detected in most ares of brain. ASIC4 is the most divergent member of ASIC family showing only 45% identity with ASIC1-3. ASIC is not activated by low pH, and my associate with other ASICs to form a functional channel.

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

M= Mouse; R=Rat; H=Human; Ha=Hamster; Rb=Rabbit; B=Bovine; C=Chicken; D=DOG; CT= near C-terminus; NT=near N-terminus; I=Middle of protein; CL=Cytoplasmic loop; EC=Extracellular domain; IC=Intracellular domain.

"Neat Antisera" are the unpurified antiserum and it is suitable for ELISA and Western.
"Affinity pure" IgG may be more suitable for immunohistochemical applications and to reduce background in most immunological applications.
"Control peptides" can not be used for Western as they are very short peptides. They are intended for ELISA or antibody blocking studies to establish antibody specificity.

All Products are for in vitro research use only.