ATTENUATION OF HYPOXIC CURRENT BY INTRACELLULAR APPLICATIONS OF ATP REGENERATING AGENTS IN HIPPOCAMPAL CA1 NEURONS OF RAT-BRAIN SLICES

Hypoxia-induced outward currents (hyperpolarization) were examined in hippocampal CA1 neurons of rat brain slices, using the whole-cell reco rding technique. Hypoxic episodes were induced by perfusing slices wit h an artificial cerebrospinal fluid aerated with 5% CO2/95% N-2 rather than 5% CO2/95% O-2, for about 3 min. The hypoxic current was consist ently and reproducibly induced in CA1 neurons dialysed with an ATP-fre e patch pipette solution. This current manifested as an outward shift in the holding current in association with increased conductance, and it reversed at - 78 +/- 2.5 mV, with a linear I-V relation in the rang e of - 100 to - 40 mV. To provide extra energy resources to individual neurons recorded, agents were added to the patch pipette solution; in cluding MgATP alone, MgATP+phosphocreatine+creatine kinase, or MgATP+c reatine. In CA1 neurons dialysed with patch solutions including these agents, hypoxia produced small outward currents in comparison with tho se observed in CA1 neurons dialysed with the ATP-free solution. Among the above agents examined, whole-cell dialysis with MgATP+creatine was the most effective at decreasing the hypoxic outward currents. We sug gest that the hypoxic hyperpolarization is closely related to energy m etabolism in individual CA1 neurons, and that the energy supply provid ed by phosphocreatine metabolism may play a critical role during trans ient metabolic stress. (C) 1998 IBRO. Published by Elsevier Science Lt d.