Identification and Functional Characterization of the Promoter of the Mouse Sodium-Activated Sodium Channel Nax Gene (Scn7a)

Na-x is a sodium channel, thought to be a descendant of the voltage-gated sodium channel family. Nevertheless, Na-x is not activated by voltage but rather by augmentation of extracellular sodium over 150 mM. In the brain, it is localized to the circumventricular organs, important regions for salt and water homeostasis in mammals, where it operates as a sodium-level sensor of body fluid. Na-x channel is expressed in lung, uterus, and heart, and it is also found in trigeminal and dorsal root ganglia and in nonmyelinating Schwann cells, where its physiological role remains unclarified. Here we identified the promoter and transcription start sites of Na-x sodium channel in dorsal root ganglia neurons from mouse. We report a characterization of the basal TATA-less promoter and the sequence requirements for promoter activity in Neuro 2A neuroblastoma cells and in dorsal root ganglia neurons, where basal promoter activity seems to require NGFI-C and Ebox DNA elements. Finally, we provide evidence that a repression mechanism that inhibits Na-x expression may be present in certain tissues. These findings provide the basis with which to understand tissue-specific regulation of Na-x sodium channel gene (Scn7a) expression. (C) 2009 Wiley-Liss, Inc.