{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:33:28Z","timestamp":1790912008999,"version":"4.1.0"},"reference-count":45,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[1998,1,1]]},"abstract":"<jats:p> Fukuda, Atsuo, Kanji Muramatsu, Akihito Okabe, Yasunobu Shimano, Hideki Hida, Ichiro Fujimoto, and Hitoo Nishino. Changes in intracellular Ca<jats:sup>2+<\/jats:sup> induced by GABA<jats:sub>A<\/jats:sub> receptor activation and reduction in Cl<jats:sup>\u2212<\/jats:sup> gradient in neonatal rat neocortex. J. Neurophysiol. 79: 439\u2013446, 1998. We have studied the effects of \u03b3-aminobutyric acid (GABA) and of reducing the Cl<jats:sup>\u2212<\/jats:sup> gradient on the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in pyramidal neurons of rat somatosensory cortex. The Cl<jats:sup>\u2212<\/jats:sup> gradient was reduced either with furosemide or by oxygen-glucose deprivation. Immature slices taken at postnatal day (P)7\u201314 were labeled with fura-2, and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> was monitored in identified pyramidal cells in layer II\/III as the ratio of fluorescence intensities (R<jats:sub>F340\/F380<\/jats:sub>). The magnitude of the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> increases induced by oxygen-glucose deprivation was significantly reduced (by 44%) by bicuculline (10 \u03bcM), a GABA<jats:sub>A<\/jats:sub> receptor antagonist. Under normal conditions, GABA generally did not raise [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, although in some neurons a small and transient [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> increase was observed. These transient [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> increases were blocked by Ni<jats:sup>2+<\/jats:sup> (1 mM), a blocker of voltage-dependent Ca<jats:sup>2+<\/jats:sup> channels (VDCCs). Continuous perfusion with GABA did not cause a sustained elevation of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> but bicuculline caused [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> oscillations. After inhibition of Cl<jats:sup>\u2212<\/jats:sup> extrusion with furosemide (1.5 mM), GABA induced a large [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> increase consisting of an initial peak followed by a sustained phase. Both the initial and the sustained phases were eliminated by bicuculline (10 \u03bcM). The initial but not the sustained phase was abolished by Ni<jats:sup>2+<\/jats:sup>. In the presence of Ni<jats:sup>2+<\/jats:sup>, the remaining sustained response was inhibited by the addition of 2-amino-5-phosphonopentanoic acid (AP5, 20 \u03bcM), a selective N-methyl-d-aspartate (NMDA) receptor antagonist. Thus the initial peak and the sustained phase of the GABA-evoked [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> increase were mediated by Ca<jats:sup>2+<\/jats:sup> influx through VDCCs and NMDA receptor channels, respectively, and both phases were initiated via the GABA<jats:sub>A<\/jats:sub> receptor. These results indicate that, in neocortical pyramidal neurons, a reduction in the Cl<jats:sup>\u2212<\/jats:sup> gradient converts the GABA<jats:sub>A<\/jats:sub> receptor-mediated action from nothing or virtually nothing to a large and sustained accumulation of cellular Ca<jats:sup>2+<\/jats:sup>. This accumulation is the result of Ca<jats:sup>2+<\/jats:sup> influx mainly through the NMDA receptor channel. Thus GABA, normally an inhibitory transmitter, may play an aggravating role in excitotoxicity if a shift in the Cl<jats:sup>\u2212<\/jats:sup> equilibrium potential occurs, as reported previously, during cerebral ischemia. <\/jats:p>","DOI":"10.1152\/jn.1998.79.1.439","type":"journal-article","created":{"date-parts":[[2017,12,25]],"date-time":"2017-12-25T07:16:33Z","timestamp":1514186193000},"page":"439-446","source":"Crossref","is-referenced-by-count":88,"title":["Changes in Intracellular Ca<sup>2+<\/sup> Induced by GABA<sub>A<\/sub> Receptor Activation and Reduction in Cl<sup>\u2212<\/sup> Gradient in Neonatal Rat Neocortex"],"prefix":"10.1152","volume":"79","author":[{"given":"Atsuo","family":"Fukuda","sequence":"first","affiliation":[{"name":"Department of Physiology, Nagoya City University Medical School, Nagoya, Aichi 467, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanji","family":"Muramatsu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nagoya City University Medical School, Nagoya, Aichi 467, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihito","family":"Okabe","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nagoya City University Medical School, Nagoya, Aichi 467, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunobu","family":"Shimano","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nagoya City University Medical School, Nagoya, Aichi 467, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Hida","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nagoya City University Medical School, Nagoya, Aichi 467, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nagoya City University Medical School, Nagoya, Aichi 467, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoo","family":"Nishino","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nagoya City University Medical School, Nagoya, Aichi 467, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(91)90003-D"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.10-08-02493.1990"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.07-05-01384.1987"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1993.70.1.448"},{"key":"B5","first-page":"2152","volume":"22","author":"Fukuda A.","year":"1996","journal-title":"Soc. 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