Abstract
The amiloride-sensitive epithelial Na+ channel (ENaC) controls Na+ transport into cells and across epithelia. So far, four homologous subunits of mammalian ENaC have been isolated and denoted as α, β, γ, and δ. ENaCδ can associate with β and γ subunits and generate a constitutive current two orders magnitude larger than that of homomeric ENaCδ. However, the distribution pattern of ENaCδ is not consistent with that of β and γ subunits. ENaCδ is expressed mainly in the brain in contrast to β and γ subunits which are expressed in non-neuronal tissues. To explain this discrepancy, we searched for novel functional properties of homomeric ENaCδ and investigated the detailed tissue distribution in humans. When hENaCδ was expressed in Xenopus oocytes and CHO cells, a reduction of extracellular pH activated this channel and the acid-induced current was abolished by amiloride. The most striking finding was that the desensitization of the acid-evoked current was much slower, dissociating from the kinetics of acid-sensing ion channels (ASICs) in degenerin/ENaC family. RNA dot-blot analyses showed that ENaCδ mRNA was widely distributed throughout the brain, and was also expressed in the heart, kidney, and pancreas in humans. Northern blotting confirmed that ENaCδ was expressed in the cerebellum and the hippocampus. In conclusion, hENaCδ activity is regulated by protons, indicating that it may contribute to the pH-sensation or/and pH-regulation in human brain. [Jpn J Physiol 54 Suppl:S134 (2004)]
