Kainate receptor-mediated inhibition of presynaptic Ca2+ influx and EPSP in area CA1 of the rat hippocampus

Abstract

1. The effect of a low concentration (1 μM) of kainate (kainic acid; KA) on presynaptic calcium (Ca2+) influx at the Schaffer collateral-commissural (SCC) synapse was examined in rat hippocampal slices. 2. Following selective loading of the presynaptic terminals with the fluorescent Ca2+ indicator rhod-2 AM, transient increases in the presynaptic Ca2+ concentration (pre[Ca2+](t)) and field excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of the SCC pathway were recorded simultaneously. 3. Bath application of 1 μM KA reversibly suppressed field EPSPs and pre[Ca2+](t) to 37.7 ± 4.0% and 72.9 ± 2.4% of control, respectively. Excitatory postsynaptic currents (EPSCs) recorded with the use of the whole-cell patch-clamp technique were also suppressed by 1 μM KA to 42.6 ± 6.3% of control. A quantitative analysis of the decreases in pre[Ca2+](t) and the amplitude of field EPSP during KA application suggests that KA inhibits transmission primarily by reducing the pre[Ca2+](t). 4. Consistent with a presynaptic site for these effects, paired-pulse facilitation (PPF) was enhanced by 1 μM KA. 5. A substantial KA-induced suppression of NMDA receptor-mediated EPSPs was detected when AMPA receptors were blocked by the AMPA receptor-selective antagonist GYKI 52466 (100 μM). 6. The suppressive effect of KA on field EPSPs and pre[Ca2+](t) was antagonized by the KA antagonist NS-102 (10 μM). 7. These results suggest that the presynaptic inhibitory action of KA at the hippocampal CA1 synapse is primarily due to the inhibition of Ca2+ influx into the presynaptic terminals.