Oxygen-sensitivity of Potassium Fluxes across Plasma Membrane of Cerebellar Granule Cells

摘要

This study focuses on the oxygen-dependence of active and passive K~+fluxes across membranes ofcerebellar granule cells of neonatal rats. Maximal Na~+,K~+-ATPase activity along with minimal passive K~+influxwas observed within oxygen concentration range characteristic for neonatal rat cerebellum. Prolonged exposureto 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. Thiswas accomplished by suppression of Na~+,K~+-ATPase with subsequent reduction in ATP consumption concur-rently with the reduction in passive K~+flux. Activation of the Na~+,K~+-ATPase by NO at physiological pO_2couldbe abolished by inhibition of NO synthase by L-NAME or soluble guanylyl cyclase with ODQ. However, treat-ment 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 al isoform of theNa~+,K~+-ATPase catalytic subunit, whereas α2/3 isoform was predominantly active under conditions of severehypoxia. We conclude that both hypoxia and hyperoxia trigger a gradual dissipation of transmembrane K~+ gra-dient and loss of excitability of cerebellar neurons. The latter may be partially reversed by suppression of NOproduction under hypoxic conditions.