Intravenously administered cell-permeant calcium buffer decreases evoked synaptic potentials in rat dentate gyms in vivo

We examined the effects of the neuroprotective cell-permeant Ca²⁺ buffer, 2-aminophenol-N,N,O-triacetic acid acetoxymethyl ester (APTRA-AM, 20- 40 mg/kg), on synaptically evoked potentials in the dentate gyrus of awake rots. Intravenous APTRA-AM (20 mg/kg) decreased the evoked potentials with peak effects ≃ 6 h after infusion, and recovery to control levels by 24 h. Peak decrease in the population spike (PS) amplitude was by 72 ± 17% of control, and the excitatory postsynaptic potential (EPSP) slope was decreased by 31 ± 12%. APTRA-AM (40 mg/kg), decreased the PS amplitude and EPSP slope by 58 ± 7% and 31 ± 6% of pre-drug levels, respectively. These effects were qualitatively similar to the presynaptically mediated decreases in synaptic potentials previously demonstrated in vitro with APTRA-AM. These results indicate that the cell-permeant Ca²⁺ buffer, APTRA-AM, attenuates hippocampal excitability in vivo, most likely by decreasing synaptic neurotransmission.