Anoxia blocks the presynaptic control of GABA release at inhibitory terminals in the rat hippocampus

Field potential and (K+)o recordings were made in rat hippocampal slices during application of 4-aminopyridine (50 microM) and ionotropic excitatory amino acid receptor antagonists, to establish whether anoxia modified the mechanisms that regulate GABA release from inhibitory interneurons. Synchronous, negative-going field potentials (amplitude = 1.41 +/- 0.64 mV, mean +/- S.D.; interval = 40.9 +/- 15.7 s; n = 10) occurred spontaneously in the CA3 stratum radiatum under control conditions. These events were associated with transient elevations in (K+)o (peak values = 5.3 +/- 0.7 mM; duration = 23.4 +/- 3.5 s; n = 5 slices) and were abolished by the GABAA, receptor antagonist bicuculline methiodide (10 microM; n = 5), the GABAB receptor agonist baclofen (100 microM; n = 6) or the mu-opioid receptor agonist (D-Ala2-N-Me-Phe, Gly-ol)enkephalin (10 microM; n = 4). Hence they represented monosynaptic field inhibitory postsynaptic potentials. Brief (4-5 min) episodes of anoxia induced a reversible, slow elevation of the baseline (K+)o to 5.2 +/- 0.3 mM (n = 5), while the rate of the field inhibitory postsynaptic potentials increased by an average of 130.7% (n = 10). Oxygen interruption during application of either baclofen (n = 6) or (D-Ala2-N-Me-Phe,Gly-ol)enkephalin (n = 4) blocked the depressant action of both drugs on the field inhibitory postsynaptic potential. These findings demonstrate that hippocampal monosynaptic field inhibitory postsynaptic potentials are resistant to brief anoxic episodes and that oxygen deprivation readily blocks the presynaptic control of GABA release exerted by GABAB and mu-opioid receptors at inhibitory interneuron terminals.