10.1007/s11827-008-1005-8

This study focuses on the oxygen-dependence of active and passive K+ fluxes across membranes of cerebellar granule cells of neonatal rats. Maximal Na+,K+-ATPase activity along with minimal passive K+ influx was observed within oxygen concentration range characteristic for neonatal rat cerebellum. Prolonged exposure to hypoxia as well as hyperoxia resulted in suppression of the Na+,K+-ATPase and activation of the passive K+ flux. Toxic effects of hypoxia could be partially prevented by inhibition of NO production with L-NAME. This was accomplished by suppression of Na+,K+-ATPase with subsequent reduction in ATP consumption concurrently with the reduction in passive K+ flux. Activation of the Na+,K+-ATPase by NO at physiological pO2 could be abolished by inhibition of NO synthase by L-NAME or soluble guanylyl cyclase with ODQ. However, treatment of cells with activator of PKG Rp-8-CTP did not mimic normoxic activation of the active K+ influx. Oxygen-induced responses under normoxic conditions were differentially mediated by α1 isoform of the Na+,K+-ATPase catalytic subunit, whereas α2/3 isoform was predominantly active under conditions of severe hypoxia. We conclude that both hypoxia and hyperoxia trigger a gradual dissipation of transmembrane K+ gradient and loss of excitability of cerebellar neurons. The latter may be partially reversed by suppression of NO production under hypoxic conditions