{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:10:51Z","timestamp":1793149851451,"version":"4.5.0"},"reference-count":76,"publisher":"Springer Science and Business Media LLC","issue":"16","license":[{"start":{"date-parts":[[2013,7,23]],"date-time":"2013-07-23T00:00:00Z","timestamp":1374537600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"},{"start":{"date-parts":[[2013,7,23]],"date-time":"2013-07-23T00:00:00Z","timestamp":1374537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO J"],"published-print":{"date-parts":[[2013,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Brain carbonic anhydrases (CAs) are known to modulate neuronal signalling. Using a novel CA VII (\n                    <jats:italic>Car7<\/jats:italic>\n                    ) knockout (KO) mouse as well as a CA II (\n                    <jats:italic>Car2<\/jats:italic>\n                    ) KO and a CA II\/VII double KO, we show that mature hippocampal pyramidal neurons are endowed with two cytosolic isoforms. CA VII is predominantly expressed by neurons starting around postnatal day 10 (P10). The ubiquitous isoform II is expressed in neurons at P20. Both isoforms enhance bicarbonate\u2010driven GABAergic excitation during intense GABA\n                    <jats:sub>A<\/jats:sub>\n                    \u2010receptor activation. P13\u201314 CA VII KO mice show behavioural manifestations atypical of experimental febrile seizures (eFS) and a complete absence of electrographic seizures. A low dose of diazepam promotes eFS in P13\u2013P14 rat pups, whereas seizures are blocked at higher concentrations that suppress breathing. Thus, the respiratory alkalosis\u2010dependent eFS are exacerbated by GABAergic excitation. We found that CA VII mRNA is expressed in the human cerebral cortex before the age when febrile seizures (FS) occur in children. Our data indicate that CA VII is a key molecule in age\u2010dependent neuronal pH regulation with consequent effects on generation of FS.\n                  <\/jats:p>","DOI":"10.1038\/emboj.2013.160","type":"journal-article","created":{"date-parts":[[2013,7,23]],"date-time":"2013-07-23T10:23:35Z","timestamp":1374575015000},"page":"2275-2286","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["Neuronal carbonic anhydrase VII provides GABAergic excitatory drive to exacerbate febrile seizures"],"prefix":"10.1038","volume":"32","author":[{"given":"Eva","family":"Ruusuvuori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje K","family":"Huebner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya","family":"Kirilkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey Y","family":"Yukin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Blaesse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Helmy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo Jung","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malek","family":"El Muayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Christopher Hennings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Voipio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nenad","family":"\u0160estan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian A","family":"H\u00fcbner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kaila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,7,23]]},"reference":[{"key":"BFEMBJ2013160_CR1","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.neuropharm.2011.06.010","volume":"61","author":"R Aamand","year":"2011","unstructured":"Aamand R, Skewes J, Moller A, Fago A, Roepstorff A (2011) Enhancing effects of acetazolamide on neuronal activity correlate with enhanced visual processing ability in humans. Neuropharmacology 61: 900\u2013908","journal-title":"Neuropharmacology"},{"key":"BFEMBJ2013160_CR2","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1113\/jphysiol.1982.sp014256","volume":"328","author":"BE Alger","year":"1982","unstructured":"Alger BE, Nicoll RA (1982) Pharmacological evidence for two kinds of GABA receptor on rat hippocampal pyramidal cells studied in vitro. J Physiol 328: 125\u2013141","journal-title":"J Physiol"},{"key":"BFEMBJ2013160_CR3","doi-asserted-by":"crossref","unstructured":"Appleton R, Macleod S, Martland T (2008) Drug management for acute tonic\u2010clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst Rev CD001905","DOI":"10.1002\/14651858.CD001905.pub2"},{"key":"BFEMBJ2013160_CR4","doi-asserted-by":"crossref","first-page":"13508","DOI":"10.1074\/jbc.M700066200","volume":"282","author":"HM Becker","year":"2007","unstructured":"Becker HM, Deitmer JW (2007) Carbonic anhydrase II increases the activity of the human electrogenic Na+\/HCO3\u2212 cotransporter. J Biol Chem 282: 13508\u201313521","journal-title":"J Biol Chem"},{"key":"BFEMBJ2013160_CR5","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/j.1528-1157.1996.tb00003.x","volume":"37","author":"AT Berg","year":"1996","unstructured":"Berg AT, Shinnar S (1996) Complex febrile seizures. Epilepsia 37: 126\u2013133","journal-title":"Epilepsia"},{"key":"BFEMBJ2013160_CR6","doi-asserted-by":"crossref","first-page":"5422","DOI":"10.1093\/emboj\/cdg519","volume":"22","author":"T Boettger","year":"2003","unstructured":"Boettger T, Rust MB, Maier H, Seidenbecher T, Schweizer M, Keating DJ, Faulhaber J, Ehmke H, Pfeffer C, Scheel O, Lemcke B, Horst J, Leuwer R, Pape HC, Volkl H, H\u00fcbner CA, Jentsch TJ (2003) Loss of K\u2010Cl co\u2010transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold. EMBO J 22: 5422\u20135434","journal-title":"EMBO J"},{"key":"BFEMBJ2013160_CR7","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.biochi.2010.05.008","volume":"92","author":"F Bootorabi","year":"2010","unstructured":"Bootorabi F, Janis J, Smith E, Waheed A, Kukkurainen S, Hytonen V, Valjakka J, Supuran CT, Vullo D, Sly WS, Parkkila S (2010) Analysis of a shortened form of human carbonic anhydrase VII expressed in vitro compared to the full\u2010length enzyme. Biochimie 92: 1072\u20131080","journal-title":"Biochimie"},{"key":"BFEMBJ2013160_CR8","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.bbapap.2009.10.021","volume":"1804","author":"WF Boron","year":"2010","unstructured":"Boron WF (2010) Evaluating the role of carbonic anhydrases in the transport of HCO3\u2010\u2010related species. Biochim Biophys Acta 1804: 410\u2013421","journal-title":"Biochim Biophys Acta"},{"key":"BFEMBJ2013160_CR9","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nrm2820","volume":"11","author":"JR Casey","year":"2010","unstructured":"Casey JR, Grinstein S, Orlowski J (2010) Sensors and regulators of intracellular pH. Nat Rev Mol Cell Biol 11: 50\u201361","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFEMBJ2013160_CR10","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1152\/physrev.00010.2003","volume":"83","author":"M Chesler","year":"2003","unstructured":"Chesler M (2003) Regulation and modulation of pH in the brain. Physiol Rev 83: 1183\u20131221","journal-title":"Physiol Rev"},{"key":"BFEMBJ2013160_CR11","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1002\/1531-8249(200003)47:3<336::AID-ANA9>3.0.CO;2-W","volume":"47","author":"C Dube","year":"2000","unstructured":"Dube C, Chen K, Eghbal\u2010Ahmadi M, Brunson K, Soltesz I, Baram TZ (2000) Prolonged febrile seizures in the immature rat model enhance hippocampal excitability long term. Ann Neurol 47: 336\u2013344","journal-title":"Ann Neurol"},{"key":"BFEMBJ2013160_CR12","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/ana.20358","volume":"57","author":"C Dube","year":"2005","unstructured":"Dube C, Vezzani A, Behrens M, Bartfai T, Baram TZ (2005) Interleukin\u20101beta contributes to the generation of experimental febrile seizures. Ann Neurol 57: 152\u2013155","journal-title":"Ann Neurol"},{"key":"BFEMBJ2013160_CR13","doi-asserted-by":"crossref","first-page":"10837","DOI":"10.1021\/bi980046t","volume":"37","author":"JN Earnhardt","year":"1998","unstructured":"Earnhardt JN, Qian MZ, Tu CK, Lakkis MM, Bergenhem NCH, Laipis PJ, Tashian RE, Silverman DN (1998) The catalytic properties of murine carbonic anhydrase VII. Biochemistry 37: 10837\u201310845","journal-title":"Biochemistry"},{"key":"BFEMBJ2013160_CR14","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/40404","volume":"388","author":"M Eghbali","year":"1997","unstructured":"Eghbali M, Curmi JP, Birnir B, Gage PW (1997) Hippocampal GABA(A) channel conductance increased by diazepam. Nature 388: 71\u201375","journal-title":"Nature"},{"key":"BFEMBJ2013160_CR15","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1152\/physrev.00029.2009","volume":"90","author":"P Enyedi","year":"2010","unstructured":"Enyedi P, Czirjak G (2010) Molecular background of leak K+ currents: Two\u2010pore domain potassium channels. Physiol Rev 90: 559\u2013605","journal-title":"Physiol Rev"},{"key":"BFEMBJ2013160_CR16","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.pneurobio.2004.06.003","volume":"73","author":"M Erecinska","year":"2004","unstructured":"Erecinska M, Cherian S, Silver IA (2004) Energy metabolism in mammalian brain during development. Prog Neurobiol 73: 397\u2013445","journal-title":"Prog Neurobiol"},{"key":"BFEMBJ2013160_CR17","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0079-6123(06)60005-8","volume":"160","author":"M Farrant","year":"2007","unstructured":"Farrant M, Kaila K (2007) The cellular, molecular and ionic basis of GABAA receptor signalling. Prog Brain Res 160: 59\u201387","journal-title":"Prog Brain Res"},{"key":"BFEMBJ2013160_CR18","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1111\/j.1460-9568.2007.05543.x","volume":"25","author":"Y Fujiwara\u2010Tsukamoto","year":"2007","unstructured":"Fujiwara\u2010Tsukamoto Y, Isomura Y, Imanishi M, Fukai T, Takada M (2007) Distinct types of ionic modulation of GABA actions in pyramidal cells and interneurons during electrical induction of hippocampal seizure\u2010like network activity. Eur J Neurosci 25: 2713\u20132725","journal-title":"Eur J Neurosci"},{"key":"BFEMBJ2013160_CR19","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1152\/physrev.2000.80.2.681","volume":"80","author":"C Geers","year":"2000","unstructured":"Geers C, Gros G (2000) Carbon dioxide transport and carbonic anhydrase in blood and muscle. Physiol Rev 80: 681\u2013715","journal-title":"Physiol Rev"},{"key":"BFEMBJ2013160_CR20","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/0306-4522(80)90053-6","volume":"5","author":"MS Ghandour","year":"1980","unstructured":"Ghandour MS, Langley OK, Vincendon G, Gombos G, Filippi D, Limozin N, Dalmasso C, Laurent G (1980) Immunochemical and immunohistochemical study of carbonic anhydrase\u2010II in adult rat cerebellum\u2014a marker for oligodendrocytes. Neuroscience 5: 559\u2013571","journal-title":"Neuroscience"},{"key":"BFEMBJ2013160_CR21","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/0165-3806(95)00069-P","volume":"87","author":"T Gloveli","year":"1995","unstructured":"Gloveli T, Albrecht D, Heinemann U (1995) Properties of low Mg2+ induced epileptiform activity in rat hippocampal and entorhinal cortex slices during adolescence. Dev Brain Res 87: 145\u2013152","journal-title":"Dev Brain Res"},{"key":"BFEMBJ2013160_CR22","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1128\/MCB.26.1.182-191.2006","volume":"26","author":"M Hentschke","year":"2006","unstructured":"Hentschke M, Wiemann M, Hentschke S, Kurth I, Hermans\u2010Borgmeyer I, Seidenbecher T, Jentsch TJ, Gal A, H\u00fcbner CA (2006) Mice with a targeted disruption of the Cl\u2212\/HCO3\u2212 exchanger AE3 display a reduced seizure threshold. Mol Cell Biol 26: 182\u2013191","journal-title":"Mol Cell Biol"},{"key":"BFEMBJ2013160_CR23","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1528-1167.2010.02914.x","volume":"52","author":"EL Hill","year":"2011","unstructured":"Hill EL, Hosie S, Mulligan RS, Richards KL, Davies PJ, Dube CM, Baram TZ, Reid CA, Jones MV, Petrou S (2011) Temperature elevation increases GABA(A)\u2010mediated cortical inhibition in a mouse model of genetic epilepsy. Epilepsia 52: 179\u2013184","journal-title":"Epilepsia"},{"key":"BFEMBJ2013160_CR24","unstructured":"Hille B (2001) Ionic channels of excitable membranes Third Edition. Sunderland, Massachusetts: Sinauer Associates,"},{"key":"BFEMBJ2013160_CR25","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1146\/annurev.me.34.020183.002321","volume":"34","author":"DG Hirtz","year":"1983","unstructured":"Hirtz DG, Nelson KB (1983) The natural history of febrile seizures. Annu Rev Med 34: 453\u2013471","journal-title":"Annu Rev Med"},{"key":"BFEMBJ2013160_CR26","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1016\/j.bmcl.2008.03.012","volume":"18","author":"A Innocenti","year":"2008","unstructured":"Innocenti A, Scozzafava A, Parkkila S, Puccetti L, De Simone G, Supuran CT (2008) Investigations of the esterase, phosphatase, and sulfatase activities of the cytosolic mammalian carbonic anhydrase isoforms I, II, and XIII with 4\u2010nitrophenyl esters as substrates. Bioorg Med Chem Lett 18: 2267\u20132271","journal-title":"Bioorg Med Chem Lett"},{"key":"BFEMBJ2013160_CR27","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1073\/pnas.0705487105","volume":"105","author":"S Jacobs","year":"2008","unstructured":"Jacobs S, Ruusuvuori E, Sipila ST, Haapanen A, Damkier HH, Kurth I, Hentschke M, Schweizer M, Rudhard Y, Laatikainen LM, Tyynela J, Praetorius J, Voipio J, Hubner CA (2008) Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability. Proc Natl Acad Sci USA 105: 311\u2013316","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2013160_CR28","doi-asserted-by":"crossref","first-page":"7662","DOI":"10.1523\/JNEUROSCI.17-20-07662.1997","volume":"17","author":"K Kaila","year":"1997","unstructured":"Kaila K, Lamsa K, Smirnov S, Taira T, Voipio J (1997) Long\u2010lasting GABA\u2010mediated depolarization evoked by high\u2010 frequency stimulation in pyramidal neurons of rat hippocampal slice is attributable to a network\u2010driven, bicarbonate\u2010dependent K+ transient. J Neurosci 17: 7662\u20137672","journal-title":"J Neurosci"},{"key":"BFEMBJ2013160_CR29","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1113\/jphysiol.1989.sp017755","volume":"416","author":"K Kaila","year":"1989","unstructured":"Kaila K, Pasternack M, Saarikoski J, Voipio J (1989) Influence of GABA\u2010gated bicarbonate conductance on potential, current and intracellular chloride in crayfish muscle fibres. J Physiol 416: 161\u2013181","journal-title":"J Physiol"},{"key":"BFEMBJ2013160_CR30","unstructured":"Kaila K, Ransom BR (1998) pH and Brain Function New York: Wiley\u2010Liss, Inc.,"},{"key":"BFEMBJ2013160_CR31","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1113\/jphysiol.1990.sp018170","volume":"427","author":"K Kaila","year":"1990","unstructured":"Kaila K, Saarikoski J, Voipio J (1990) Mechanism of action of GABA on intracellular pH and on surface pH in crayfish muscle fibres. J Physiol 427: 241\u2013260","journal-title":"J Physiol"},{"key":"BFEMBJ2013160_CR32","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/330163a0","volume":"330","author":"K Kaila","year":"1987","unstructured":"Kaila K, Voipio J (1987) Postsynaptic fall in intracellular pH induced by GABA\u2010activated bicarbonate conductance. Nature 330: 163\u2013165","journal-title":"Nature"},{"key":"BFEMBJ2013160_CR33","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/nature10523","volume":"478","author":"HJ Kang","year":"2011","unstructured":"Kang HJ et al (2011) Spatio\u2010temporal transcriptome of the human brain. Nature 478: 483\u2013489","journal-title":"Nature"},{"key":"BFEMBJ2013160_CR34","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/0306-3623(90)90829-B","volume":"21","author":"ML Laorden","year":"1990","unstructured":"Laorden ML, Carrillo E, Miralles FS, Puig MM (1990) Effects of diltiazem on hyperthermia induced seizures in the rat pup. Gen Pharmacol 21: 313\u2013315","journal-title":"Gen Pharmacol"},{"key":"BFEMBJ2013160_CR35","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1006\/excr.1998.4071","volume":"242","author":"P Lehenkari","year":"1998","unstructured":"Lehenkari P, Hentunen TA, Laitala\u2010Leinonen T, Tuukkanen J, Vaananen HK (1998) Carbonic anhydrase II plays a major role in osteoclast differentiation and bone resorption by effecting the steady state intracellular pH and Ca2+. Exp Cell Res 242: 128\u2013137","journal-title":"Exp Cell Res"},{"key":"BFEMBJ2013160_CR36","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1073\/pnas.85.6.1962","volume":"85","author":"SE Lewis","year":"1988","unstructured":"Lewis SE, Erickson RP, Barnett LB, Venta PJ, Tashian RE (1988) N\u2010ethyl\u2010N\u2010nitrosurea induced mutation at the mouse Car\u20102 locus \u2010 an animal model for human carbonic anhydrase II\u2010deficiency syndrome. Proc Natl Acad Sci USA 85: 1962\u20131966","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2013160_CR37","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1152\/jn.1997.77.4.1844","volume":"77","author":"M Luckermann","year":"1997","unstructured":"Luckermann M, Trapp S, Ballanyi K (1997) GABA\u2010 and glycine\u2010mediated fall of intracellular pH in rat medullary neurons in situ. J Neurophysiol 77: 1844\u20131852","journal-title":"J Neurophysiol"},{"key":"BFEMBJ2013160_CR38","doi-asserted-by":"crossref","first-page":"8270","DOI":"10.1073\/pnas.1205902109","volume":"109","author":"VA Magnotta","year":"2012","unstructured":"Magnotta VA, Heo HY, Dlouhy BJ, Dahdaleh NS, Follmer RL, Thedens DR, Welsh MJ, Wemmie JA (2012) Detecting activity\u2010evoked pH changes in human brain. Proc Natl Acad Sci USA 109: 8270\u20138273","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2013160_CR39","doi-asserted-by":"crossref","first-page":"16754","DOI":"10.1523\/JNEUROSCI.1467-12.2012","volume":"32","author":"S Makani","year":"2012","unstructured":"Makani S, Chen HY, Esquenazi S, Shah GN, Waheed A, Sly WS, Chesler M (2012) NMDA receptor\u2010dependent afterdepolarizations are curtailed by carbonic anhydrase 14: regulation of a short\u2010term postsynaptic potentiation. J Neurosci 32: 16754\u201316762","journal-title":"J Neurosci"},{"key":"BFEMBJ2013160_CR40","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1146\/annurev.genet.35.102401.091142","volume":"35","author":"MH Meisler","year":"2001","unstructured":"Meisler MH, Kearney J, Ottman R, Escayg A (2001) Identification of epilepsy genes in human and mouse. Annu Rev Genet 35: 567\u2013588","journal-title":"Annu Rev Genet"},{"key":"BFEMBJ2013160_CR41","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1469-7793.1999.0493m.x","volume":"519","author":"T Munsch","year":"1999","unstructured":"Munsch T, Pape HC (1999) Modulation of the hyperpolarization\u2010activated cation current of rat thalamic relay neurones by intracellular pH. J Physiol 519Pt 2: 493\u2013504","journal-title":"J Physiol"},{"key":"BFEMBJ2013160_CR42","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/j.1469-8749.1999.tb00613.x","volume":"41","author":"E Norris","year":"1999","unstructured":"Norris E, Marzouk O, Nunn A, McIntyre J, Choonara I (1999) Respiratory depression in children receiving diazepam for acute seizures: a prospective study. Dev Med Child Neurol 41: 340\u2013343","journal-title":"Dev Med Child Neurol"},{"key":"BFEMBJ2013160_CR43","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/S0196-0644(05)82981-6","volume":"20","author":"RA Orr","year":"1991","unstructured":"Orr RA, Dimand RJ, Venkataraman ST, Karr VA, Kennedy KJ (1991) Diazepam and intubation in emergency treatment of seizures in children. Ann Emerg Med 20: 1009\u20131013","journal-title":"Ann Emerg Med"},{"key":"BFEMBJ2013160_CR44","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/S0028-3908(96)00075-5","volume":"35","author":"M Pasternack","year":"1996","unstructured":"Pasternack M, Smirnov S, Kaila K (1996) Proton modulation of functionally distinct GABAA receptors in acutely isolated pyramidal neurons of rat hippocampus. Neuropharmacology 35: 1279\u20131288","journal-title":"Neuropharmacology"},{"key":"BFEMBJ2013160_CR45","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1748-1716.1993.tb09553.x","volume":"148","author":"M Pasternack","year":"1993","unstructured":"Pasternack M, Voipio J, Kaila K (1993) Intracellular carbonic anhydrase activity and its role in GABA\u2010induced acidosis in isolated rat hippocampal pyramidal neurones. Acta Physiol Scand 148: 229\u2013231","journal-title":"Acta Physiol Scand"},{"key":"BFEMBJ2013160_CR46","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/sj.bjp.0703825","volume":"132","author":"P Pickkers","year":"2001","unstructured":"Pickkers P, Hughes AD, Russel FG, Thien T, Smits P (2001) In vivo evidence for K(Ca) channel opening properties of acetazolamide in the human vasculature. Br J Pharmacol 132: 443\u2013450","journal-title":"Br J Pharmacol"},{"key":"BFEMBJ2013160_CR47","doi-asserted-by":"crossref","first-page":"8145","DOI":"10.1073\/pnas.87.20.8145","volume":"87","author":"N Qian","year":"1990","unstructured":"Qian N, Sejnowski TJ (1990) When is an inhibitory synapse effective? Proc Natl Acad Sci USA 87: 8145\u20138149","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2013160_CR48","doi-asserted-by":"crossref","first-page":"15638","DOI":"10.1523\/JNEUROSCI.3355-10.2010","volume":"30","author":"E Ruusuvuori","year":"2010","unstructured":"Ruusuvuori E, Kirilkin I, Pandya N, Kaila K (2010) Spontaneous network events driven by depolarizing GABA action in neonatal hippocampal slices are not attributable to deficient mitochondrial energy metabolism. J Neurosci 30: 15638\u201315642","journal-title":"J Neurosci"},{"key":"BFEMBJ2013160_CR49","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1523\/JNEUROSCI.5176-03.2004","volume":"24","author":"E Ruusuvuori","year":"2004","unstructured":"Ruusuvuori E, Li H, Huttu K, Palva JM, Smirnov S, Rivera C, Kaila K, Voipio J (2004) Carbonic anhydrase isoform VII acts as a molecular switch in the development of synchronous gamma\u2010frequency firing of hippocampal CA1 pyramidal cells. J Neurosci 24: 2699\u20132707","journal-title":"J Neurosci"},{"key":"BFEMBJ2013160_CR50","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1111\/j.1528-1167.2011.03259.x","volume":"52","author":"S Schuchmann","year":"2011","unstructured":"Schuchmann S, Hauck S, Henning S, Gruters\u2010Kieslich A, Vanhatalo S, Schmitz D, Kaila K (2011) Respiratory alkalosis in children with febrile seizures. Epilepsia 52: 1949\u20131955","journal-title":"Epilepsia"},{"key":"BFEMBJ2013160_CR51","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/nm1422","volume":"12","author":"S Schuchmann","year":"2006","unstructured":"Schuchmann S, Schmitz D, Rivera C, Vanhatalo S, Salmen B, Mackie K, Sipil\u00e4 ST, Voipio J, Kaila K (2006) Experimental febrile seizures are precipitated by a hyperthermia\u2010induced respiratory alkalosis. Nat Med 12: 817\u2013823","journal-title":"Nat Med"},{"key":"BFEMBJ2013160_CR52","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.braindev.2008.11.011","volume":"31","author":"S Schuchmann","year":"2009","unstructured":"Schuchmann S, Vanhatalo S, Kaila K (2009) Neurobiological and physiological mechanisms of fever\u2010related epileptiform syndromes. Brain Dev 31: 378\u2013382","journal-title":"Brain Dev"},{"key":"BFEMBJ2013160_CR53","doi-asserted-by":"crossref","first-page":"7300","DOI":"10.1523\/JNEUROSCI.0269-11.2011","volume":"31","author":"A Sinning","year":"2011","unstructured":"Sinning A, Liebmann L, Kougioumtzes A, Westermann M, Bruehl C, Hubner CA (2011) Synaptic glutamate release is modulated by the Na+\u2010driven Cl\u2212\/HCO3\u2212 exchanger Slc4a8. J Neurosci 31: 7300\u20137311","journal-title":"J Neurosci"},{"key":"BFEMBJ2013160_CR54","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1126\/science.6779379","volume":"211","author":"DC Spray","year":"1981","unstructured":"Spray DC, Harris AL, Bennet MVL (1981) Gap junctional conductance is a simple and sensitive function of intracellular pH. Science 211: 712\u2013715","journal-title":"Science"},{"key":"BFEMBJ2013160_CR55","doi-asserted-by":"crossref","unstructured":"Stafstrom CE (2002) The incidence and prevalence of febrile seizures. In:Febrile seizures Baram TZ, Shinnar S (eds). pp1\u201325.Academic Press: San Diego,","DOI":"10.1016\/B978-012078141-6\/50003-2"},{"key":"BFEMBJ2013160_CR56","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1126\/science.7638623","volume":"269","author":"KJ Staley","year":"1995","unstructured":"Staley KJ, Soldo BL, Proctor WR (1995) Ionic mechanisms of neuronal excitation by inhibitory GABA(A) receptors. Science 269: 977\u2013981","journal-title":"Science"},{"key":"BFEMBJ2013160_CR57","doi-asserted-by":"crossref","first-page":"47886","DOI":"10.1074\/jbc.M105959200","volume":"276","author":"D Sterling","year":"2001","unstructured":"Sterling D, Reithmeier RAF, Casey JR (2001) A transport metabolon. Functional interaction of carbonic anhydrase II and chloride\/bicarbonate exchangers. J Biol Chem 276: 47886\u201347894","journal-title":"J Biol Chem"},{"key":"BFEMBJ2013160_CR58","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1113\/jphysiol.2011.220152","volume":"590","author":"MH Stridh","year":"2012","unstructured":"Stridh MH, Alt MD, Wittmann S, Heidtmann H, Aggarwal M, Riederer B, Seidler U, Wennemuth G, McKenna R, Deitmer JW, Becker HM (2012) Lactate flux in astrocytes is enhanced by a non\u2010catalytic action of carbonic anhydrase II. J Physiol 590: 2333\u20132351","journal-title":"J Physiol"},{"key":"BFEMBJ2013160_CR59","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrd2467","volume":"7","author":"CT Supuran","year":"2008","unstructured":"Supuran CT (2008) Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat Rev Drug Discov 7: 168\u2013181","journal-title":"Nat Rev Drug Discov"},{"key":"BFEMBJ2013160_CR60","doi-asserted-by":"crossref","first-page":"4680","DOI":"10.1523\/JNEUROSCI.13-11-04680.1993","volume":"13","author":"JW Swann","year":"1993","unstructured":"Swann JW, Smith KL, Brady RJ (1993) Localized excitatory synaptic\u2010interactions mediate the sustained depolarization of electrographic seizures in developing hippocampus. J Neurosci 13: 4680\u20134689","journal-title":"J Neurosci"},{"key":"BFEMBJ2013160_CR61","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1136\/adc.79.1.78","volume":"79","author":"RC Tasker","year":"1998","unstructured":"Tasker RC (1998) Emergency treatment of acute seizures and status epilepticus. Arch Dis Child 79: 78\u201383","journal-title":"Arch Dis Child"},{"key":"BFEMBJ2013160_CR62","doi-asserted-by":"crossref","first-page":"855","DOI":"10.2174\/156802607780636726","volume":"7","author":"A Thiry","year":"2007","unstructured":"Thiry A, Dogne J, Supuran CT, Masereel B (2007) Carbonic anhydrase inhibitors as anticonvulsant agents. Curr Top Med Chem 7: 855\u2013864","journal-title":"Curr Top Med Chem"},{"key":"BFEMBJ2013160_CR63","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1528-1167.2010.02731.x","volume":"52","author":"EA Tolner","year":"2011","unstructured":"Tolner EA, Hochman DW, Hassinen P, Otahal J, Gaily E, Haglund MM, Kubova H, Schuchmann S, Vanhatalo S, Kaila K (2011) Five percent CO2 is a potent, fast\u2010acting inhalation anticonvulsant. Epilepsia 52: 104\u2013114","journal-title":"Epilepsia"},{"key":"BFEMBJ2013160_CR64","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1124\/pr.109.002451","volume":"62","author":"SF Traynelis","year":"2010","unstructured":"Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R (2010) Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 62: 405\u2013496","journal-title":"Pharmacol Rev"},{"key":"BFEMBJ2013160_CR65","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1016\/j.bmcl.2011.12.134","volume":"22","author":"E Truppo","year":"2012","unstructured":"Truppo E, Supuran CT, Sandomenico A, Vullo D, Innocenti A, Di FA, Alterio V, De SG, Monti SM (2012) Carbonic anhydrase VII is S\u2010glutathionylated without loss of catalytic activity and affinity for sulfonamide inhibitors. Bioorg Med Chem Lett 22: 1560\u20131564","journal-title":"Bioorg Med Chem Lett"},{"key":"BFEMBJ2013160_CR66","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/j.1601-183X.2008.00393.x","volume":"7","author":"KL van Gassen","year":"2008","unstructured":"van Gassen KL, Hessel EV, Ramakers GM, Notenboom RG, Wolterink\u2010Donselaar IG, Brakkee JH, Godschalk TC, Qiao X, Spruijt BM, van NO, De Graan PN (2008) Characterization of febrile seizures and febrile seizure susceptibility in mouse inbred strains. Genes Brain Behav 7: 578\u2013586","journal-title":"Genes Brain Behav"},{"key":"BFEMBJ2013160_CR67","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/BF00243215","volume":"101","author":"L Velisek","year":"1994","unstructured":"Velisek L, Dreier JP, Stanton PK, Heinemann U, Moshe SL (1994) Lowering of extracellular pH suppresses low\u2010Mg2+ induced seizures in combined entorhinal cortex\u2010hippocampal slices. Exp Brain Res 101: 44\u201352","journal-title":"Exp Brain Res"},{"key":"BFEMBJ2013160_CR68","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1113\/jphysiol.2009.181826","volume":"588","author":"T Viitanen","year":"2010","unstructured":"Viitanen T, Ruusuvuori E, Kaila K, Voipio J (2010) The KCl \u2010cotransporter KCC2 promotes GABAergic excitation in the mature rat hippocampus. J Physiol 588: 1527\u20131540","journal-title":"J Physiol"},{"key":"BFEMBJ2013160_CR69","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/BF00374394","volume":"423","author":"J Voipio","year":"1993","unstructured":"Voipio J, Kaila K (1993) Interstitial PCO2 and pH in rat hippocampal slices measured by means of a novel fast CO2\/H+\u2010sensitive microelectrode based on a PVC\u2010gelled membrane. Pflugers Arch 423: 193\u2013201","journal-title":"Pflugers Arch"},{"key":"BFEMBJ2013160_CR70","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1242\/jeb.156.1.349","volume":"156","author":"J Voipio","year":"1991","unstructured":"Voipio J, Pasternack M, Rydqvist B, Kaila K (1991) Effect of gamma\u2010aminobutyric acid on intracellular pH in the crayfish stretch\u2010receptor neurone. J Exp Biol 156: 349\u2013360","journal-title":"J Exp Biol"},{"key":"BFEMBJ2013160_CR71","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/386173a0","volume":"386","author":"R Waldmann","year":"1997","unstructured":"Waldmann R, Champigny G, Bassilana F, Heurteaux C, Lazdunski M (1997) A proton\u2010gated cation channel involved in acid\u2010sensing. Nature 386: 173\u2013177","journal-title":"Nature"},{"key":"BFEMBJ2013160_CR72","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1113\/jphysiol.2001.013443","volume":"540","author":"WG Wang","year":"2002","unstructured":"Wang WG, Bradley SR, Richerson GB (2002) Quantification of the response of rat medullary raphe neurones to independent changes in pHO and PCO2. J Physiol 540: 951\u2013970","journal-title":"J Physiol"},{"key":"BFEMBJ2013160_CR73","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1113\/jphysiol.2005.088823","volume":"567","author":"ME Wilkins","year":"2005","unstructured":"Wilkins ME, Hosie AM, Smart TG (2005) Proton modulation of recombinant GABA(A) receptors: influence of GABA concentration and the beta subunit TM2\u2010TM3 domain. J Physiol 567: 365\u2013377","journal-title":"J Physiol"},{"key":"BFEMBJ2013160_CR74","doi-asserted-by":"crossref","first-page":"10685","DOI":"10.1073\/pnas.0702676104","volume":"104","author":"RH Williams","year":"2007","unstructured":"Williams RH, Jensen LT, Verkhratsky A, Fugger L, Burdakov D (2007) Control of hypothalamic orexin neurons by acid and CO2. Proc Natl Acad Sci USA 104: 10685\u201310690","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2013160_CR75","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1172\/JCI42219","volume":"120","author":"VC Wimmer","year":"2010","unstructured":"Wimmer VC, Reid CA, Mitchell S, Richards KL, Scaf BB, Leaw BT, Hill EL, Royeck M, Horstmann MT, Cromer BA, Davies PJ, Xu R, Lerche H, Berkovic SF, Beck H, Petrou S (2010) Axon initial segment dysfunction in a mouse model of genetic epilepsy with febrile seizures plus. J Clin Invest 120: 2661\u20132671","journal-title":"J Clin Invest"},{"key":"BFEMBJ2013160_CR76","doi-asserted-by":"crossref","unstructured":"Ruusuvuori E, Kaila K (2013) Carbonic anhydrases and brain pH in the control of neuronal excitability. InCarbonic Anhydrase: Mechanism, Regulation, Links to Disease, and Industrial Applications Frost SC, McKenna R (eds), Springer (in press","DOI":"10.1007\/978-94-007-7359-2_14"}],"container-title":["The EMBO Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Femboj.2013.160","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/emboj.2013.160.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1038\/emboj.2013.160","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/emboj.2013.160.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:33:13Z","timestamp":1779237193000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1038\/emboj.2013.160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,23]]},"references-count":76,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2013,8,14]]}},"alternative-id":["BFEMBJ2013160"],"URL":"https:\/\/doi.org\/10.1038\/emboj.2013.160","relation":{},"ISSN":["0261-4189","1460-2075"],"issn-type":[{"value":"0261-4189","type":"print"},{"value":"1460-2075","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,23]]},"assertion":[{"value":"9 January 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}