{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:37:09Z","timestamp":1790696229297,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,12,4]],"date-time":"2006-12-04T00:00:00Z","timestamp":1165190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Synapse"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intracellular Cl<jats:sup>\u2212<\/jats:sup> concentration ([Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub>) in immature neurons is higher than that expected for a passive distribution, therefore the equilibrium potential for chloride is more positive than the resting membrane potential, and the resulting GABA renders immature neurons depolarization. The higher [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> in immature neurons is thought to be attributed to the uptake of Cl<jats:sup>\u2212<\/jats:sup> mediated by NKCC1 (Na<jats:sup>+<\/jats:sup>, K<jats:sup>+<\/jats:sup>\u20102Cl<jats:sup>\u2212<\/jats:sup> cotransporter). Thus, a dysfunction of this transporter could affect synaptic development through a GABA<jats:sub>A<\/jats:sub> receptor\u2010mediated pathway. To test this possibility, we examined the effects of a Cl<jats:sup>\u2212<\/jats:sup>\u2010uptake inhibitor on the development of synaptic activities of rat neocortical neurons in culture. Chronic treatment with bumetanide at 10 \u03bcM during the culture diminished the amplitude of synaptically\u2010driven rhythmic depolarizing potentials (RDPs) in neurons and also decreased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) but not of spontaneous excitatory postsynaptic currents (sEPSCs). Chronic treatment with bumetanide decreased vesicular GABA transporter (VGAT)\u2010immunopositive particles without affecting paired\u2010pulse ratio of evoked IPSCs (eIPSCs), indicating decrease in the number of functional GABAergic synapses. Acute treatment with bumetanide (10 \u03bcM) decreased neuronal [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub>, the amplitude of RDPs, and neuronal excitability, while bumetanide had no effect on RDPs and neuronal excitability in the presence of bicuculline. These results suggest that the uptake of Cl<jats:sup>\u2212<\/jats:sup> by NKCC1 affects the development of inhibitory synapses by promoting a depolarizing GABA\u2010mediated response. Synapse 61:138\u2013149, 2007. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/syn.20352","type":"journal-article","created":{"date-parts":[[2006,12,4]],"date-time":"2006-12-04T19:02:09Z","timestamp":1165258929000},"page":"138-149","source":"Crossref","is-referenced-by-count":27,"title":["NKCC1 activity modulates formation of functional inhibitory synapses in cultured neocortical 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