A3793-01

Rabbit Anti-Mammalian Degenerin 1 (MDGE1, ASIC2, BNaC1)

Tissue acidosis that occurs in ischemia, tissue damage or inflammation is accompanied by pain. Proton-gated cation channels are activated by low pH in nociceptive neurons. H+-gated channels are members of the NaC/DEG superfamily that include: (1) Amiloride-sensitive epithelial Na+ channels (a, b, and g, and d-ENaC subunits); (2) A FMRFamide-gated channel (FaNaC), (3) and mechanosensory channel proteins of nematode degenerins (DEG). NaC/DEG superfamily is characterized by intracellular N and C-termini, two transmembrane domains, and a large extracellular loop. All members of this family are selective for Na+ and blocked by amiloride. The mammalian homolog of degenerins (MDEG or MDEG1; now designated ASIC for Acid Sensing Ion Channels). Three are at least three distinct proteins in ASIC family: ASIC1 (identical with human BNAC2 or BNC2), expressed in brain and dorsal root ganglions (DRG) cells, is activated by pH <7.0. A splice variant of rat ASIC, ASIC-beta, is expressed only in a subset of small and large diameter sensory neurons and absent in sympathetic neurons and CNS. MDEG1/ASIC2, 67% identity with ASIC1, requires more acidic pH than ASIC1 and has slower activation kinetic. MDEG2/ASIC2b), a splice variant of MDEG1, 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/ASIC3 (Dorsal Root ganglion ASIC). DRASIC 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.