Epithelial Na+ channel delta subunit mediates acid-induced ATP release in the human skin.

The amiloride-sensitive epithelial Na(+) channel (ENaC) regulates Na(+) homeostasis in cells and across epithelia. Although we described that ENaCdelta is a candidate molecule for a pH sensor in the human brain, the physiological and pathological roles of ENaCdelta in non-neuronal tissues are still unknown. Here we show a novel physiological function of ENaCdelta in peripheral tissues in humans. Expression analyses at the level of mRNA clearly revealed that ENaCdelta was abundantly expressed in human epidermis and keratinocytes. In addition, ENaCdelta protein was detected in there. In cultured keratinocytes, acidic stress (pH 5.0) evoked ATP release, which was significantly reduced in the presence of 100 microM amiloride or 10 microM benzamil. In conclusion, ENaCdelta may be involved in the mechanism underlying pH sensing followed by the regulation of cell viability in the human skin.