Tissue acidosis (decrease in pH below the physiological level) that occurs in ischemia, tissue damage or inflammation is accompanied by pain. At the molecular level, H+-gated cation channels are activated by low pH in nociceptive neurons. H+-gated cation channels, members of the NaC/DEG superfamily of Na channels that include amiloride-sensitive epithelial Na+ channel proteins (alpha, beta, and gamma, and delta-ENaC subunits), are expressed in epithelia of the vertebrate kidney, colon, lucolon and other tissues. ENaC-b from various species are ~80% identical, and only ~30% similarity with the ENaC-alpha 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.