The functional expression of the epithelial Na+ channel is necessary to permit the controlled absorption of Na+ from the lung/airway epithelia. Glucocorticoids play an important role in the development of the lungs absorbing phenotype through evoking SGK enzyme expression. These enzymes play a role in controlling the number of Na+ channels in the plasma membrane. We demonstrate in H441 cells that over expression of constitutively active SGK1 (SGK*) in the absence of glucocorticoids generates a Na+ absorbing phenotype that is potentiated by insulin. Insulin also acts to depolarise Vm.

Cells grown in dialysed media containing dexamethasone (dex) and insulin had a membrane potential (Vm ) of -27±2.7mV in normal physiological saline (PS). In low Na+o (10mM, 130mM NMDG) Vm hyperpolarised to -60±2.8mV. Slope conductance (G) of the Na+ current was 104±16ps cell-1 . In the absence of dex, in normal PS, Vm was -63±4.9mV and was unaffected by reducing Na+o. In absence of dex and insulin Vm was -83.7±-4.7mV. Transfection of SGK* (-dex/-insulin) Vm was -49.2±3.5mV which hyperpolarised to -76.6±3.5mV in low Na+o, GNa = 53±13pS cell-1 . Transfection of SGK*(-dex/+insulin) Vm was -32.2±2.9mV which hyperpolarised to -63.4±4.4mV in low Na+ o, GNa significantly increased (117±23pS cell-1 , P<0.01).