Regulation of Delta-Enac Ion Channels by the Neuronal-Specific Sgk1.1 Kinase

Abstract

The epithelial sodium channel (ENaC) is a voltage-independent ion channel that plays a fundamental role in kidney transepithelial sodium transport and extracellular volume homeostasis. Previous work from our group and others have identified a novel ENaC subunit that is prominently expressed in neurons but not in kidney epithelia. The physiological role of delta-ENaC channels in neurons is unknown, but it could be involved in the regulation of membrane resting potential and hence of neuronal excitability. Kidney ENaC activity is increased by the serum and glucocorticoid-induced kinase 1 (SGK1). Recently, a new neuronal-specific isoform of SGK1, named SGK1.1, has been identified. We have tested whether SGK1.1 regulates delta-ENaC activity. Co-injection of SGK1.1 and delta-ENaC channels in Xenopus oocytes increased sodium current by two-fold. SGK1.1 increased delta-ENaC plasma membrane expression by 1.6-fold. In situ hybridization experiments confirmed the co-expression of delta ENaC and SGK1.1 in pyramidal neurons of the human cerebral cortex, indicating that this regulation could be physiologically relevant. In summary, we have identified a new regulator of delta-ENaC ion channels that could play a role in the control of neuronal resting potential and excitability.