Mechanisms underlying the depression of evoked fast EPSCs following in vitro ischemia in rat hippocampal CA1 neurons.

The mechanisms underlying the depression of evoked fast excitatory postsyna ptic currents (EPSCs) following superfusion with medium deprived of oxygen and glucose (in vitro ischemia) for a 4-min period in hippocampal CAI neuro ns were investigated in rat brain slices. The amplitude of evoked fast EPSC s decreased by 85 +/- 7% of the control 4 min after the onset of in vitro i schemia. In contrast, the exogenous glutamate-induced inward currents were augmented, while the spontaneous miniature EPSCs obtained in the presence o f tetrodotoxin (TTX, 1 muM) did not change in amplitude during in vitro isc hemia. In a normoxic medium, a pair of fast EPSCs was elicited by paired-pu lse stimulation (40-ms interval), and the amplitude of the second fast EPSC increased to 156 +/- 24% of the first EPSC amplitude. The ratio of paired- pulse facilitation (PPF ratio) increased during in vitro ischemia. Pretreat ment of the slices with adenosine 1 (A1) receptor antagonist, 8-cyclopenthy ltheophiline (8-CPT) antagonized the depression of the fast EPSCs, in a con centration-dependent manner: in the presence of 8-CPT (1-10 muM), the ampli tude of the fast EPSCs decreased by only 20% of the control during in vitro ischemia. In addition, 8-CPT antagonized the enhancement of the PPF ratio during in vitro ischemia. A pair of presynaptic volleys and excitatory post synaptic field potentials (fEPSPs) were extracellularly recorded in a proxi mal part of the stratum radiatum in the CA1 region. The PPF ratio for the f EPSPs also increased during in vitro ischemia. On the other hand, the ampli tudes of the first and second presynaptic volley, which were abolished by T TX (0.5 muM), did not change during in vitro ischemia. The maximal slope of the Ca2+-dependent action potential of the CA3 neurons, which were evoked in the presence of 8-CPT (1 muM), nifedipine (20 muM), TTX (0.5 muM) and te traethyl ammonium chloride (20 mM), decreased by 12 +/- 6% of the control 4 min after the onset of in vitro ischemia. These results suggest that in vi tro ischemia depresses the evoked fast EPSCs mainly via the presynaptic Al receptors, and the remaining 8-CPT-resistant depression of the fast EPSCs i s probably due to a direct inhibition of the Ca2+ influx to the axon termin als.