Kainate receptor-mediated inhibition of presynaptic Ca2+ influx and EPSP in area CA1 of the rat hippocampus.
1. The effect of a low concentration (1 microM) 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 microM 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 microM 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 microM 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 microM). 6. The suppressive effect of KA on field EPSPs and pre[Ca2+]t was antagonized by the KA antagonist NS-102 (10 microM). 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.
Kamiya
H
H
Department of Physiology, Gunma University School of Medicine, Maebashi, Gunma 371-8511, Japan. hkamiya@news.sb.gunma-u.ac.jp
Ozawa
S
S
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000737:chemistry* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012235:Rhodamines; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D002118:Calcium; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D007608:Kainic Acid; D009467:Neuromuscular Depolarizing Agents; D010091:Oximes; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D012235:Rhodamines; C061950:GYKI 52466; C084273:5-nitro-6,7,8,9-tetrahydrobenzo(G)indole-2,3-dione-3-oxime; C012301:domoic acid