{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T10:12:11Z","timestamp":1768990331526,"version":"3.49.0"},"reference-count":38,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[1999,2,1]]},"abstract":"<jats:p>Synaptic activation of GABA<jats:sub>A<\/jats:sub>receptors induces neuronal uptake of Ca<jats:sup>2+<\/jats:sup>in adult rat hippocampal slices. Synaptically evoked transmembrane movements of Ca<jats:sup>2+<\/jats:sup>in the adult CNS have almost exclusively been attributed to activation of glutamate receptor channels and the consequent triggering of voltage-gated calcium channels (VGCCs). Using microelectrodes for measuring free extracellular Ca<jats:sup>2+<\/jats:sup>([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>o<\/jats:sub>) and extracellular space (ECS) volume, we show here for the first time that synaptic stimulation of \u03b3-aminobutyric acid-A (GABA<jats:sub>A<\/jats:sub>) receptors can result in a decrease in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>o<\/jats:sub>in adult rat hippocampal slices. High-frequency stimulation (100\u2013200 Hz, 0.4\u20130.5 s) applied in stratum radiatum close (\u22640.5 mm) to the recording site induced a 0.1- to 0.3-mM transient fall in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>o<\/jats:sub>from a baseline level of 1.6 mM. Concomitantly, a 30\u201340% decrease in the ECS volume was seen. Exposure of drug-na\u0131\u0308ve slices to the GABA<jats:sub>A<\/jats:sub>receptor antagonist picrotoxin (100 \u03bcM) first attenuated and only thereafter augmented the Ca<jats:sup>2+<\/jats:sup>shifts. Application of ionotropic glutamate receptor antagonists resulted in a monotonic reduction of the Ca<jats:sup>2+<\/jats:sup>response, but a large Ca<jats:sup>2+<\/jats:sup>shift persisted (60\u201370% of the original), which was attenuated by a subsequent application of picrotoxin or bicuculline. In the absence of ionotropic glutamatergic transmission, pentobarbital sodium (100 \u03bcM), an up-modulator of the GABA<jats:sub>A<\/jats:sub>receptor, strongly enhanced the activity-evoked changes in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>o<\/jats:sub>. We suggest that the underlying mechanism of GABA-induced Ca<jats:sup>2+<\/jats:sup>transients is the activation of VGCCs by bicarbonate-dependent GABA-mediated depolarizing postsynaptic potentials. Accordingly, stimulation-evoked Ca<jats:sup>2+<\/jats:sup>shifts were inhibited by the membrane-permeant inhibitor of carbonic anhydrase, ethoxyzolamide (50 \u03bcM) or in N-2-hydroxyethylpiperazine- N\u2032-2-ethanesulfonic acid (HEPES)\u2013buffered HCO<jats:sub>3<\/jats:sub>-free solution. Neuronal Ca<jats:sup>2+<\/jats:sup>uptake caused by intense synaptic activation of GABA<jats:sub>A<\/jats:sub>receptors may prove to be an important mechanism in the modulation of activity-dependent neuronal plasticity, epileptogenesis, and cell survival in the adult brain.<\/jats:p>","DOI":"10.1152\/jn.1999.81.2.811","type":"journal-article","created":{"date-parts":[[2017,12,25]],"date-time":"2017-12-25T04:55:39Z","timestamp":1514177739000},"page":"811-816","source":"Crossref","is-referenced-by-count":24,"title":["Synaptic Activation of GABA<sub>A<\/sub>Receptors Induces Neuronal Uptake of Ca<sup>2+<\/sup>in Adult Rat Hippocampal Slices"],"prefix":"10.1152","volume":"81","author":[{"given":"Anna-Maija","family":"Autere","sequence":"first","affiliation":[{"name":"Department of Biosciences, Division of Animal Physiology, University of Helsinki, FIN-00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karri","family":"Lamsa","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Division of Animal Physiology, University of Helsinki, FIN-00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Kaila","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Division of Animal Physiology, University of Helsinki, FIN-00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomi","family":"Taira","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Division of Animal Physiology, University of Helsinki, FIN-00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1982.sp014255"},{"key":"B2","first-page":"892.10","volume":"23","author":"Autere A.-M.","year":"1997","journal-title":"Soc. 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