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Article: Novel role of the Ca2+-ATPase in NMDA-induced intracellular acidification

TitleNovel role of the Ca2+-ATPase in NMDA-induced intracellular acidification
Authors
Issue Date1999
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpcell.physiology.org/
Citation
American Journal Of Physiology - Cell Physiology, 1999, v. 277 n. 4 46-4, p. C717-C727 How to Cite?
AbstractThe mechanism involved in N-methyl-D-glucamine (NMDA)-induced Ca2+dependent intracellular acidosis is not clear. In this study, we investigated in detail several possible mechanisms using cultured rat cerebellar granule cells and microfluorometry [fura 2-AM or 2',7'-bis(2- carboxyethyl)-5(6)-carboxyfluorescein-AM]. When 100 μM NMDA or 40 mM KCl was added, a marked increase in the intracellular Ca2+ concentration ([Ca2+](i)) and a decrease in the intracellular pH were seen. Acidosis was completely prevented by the use of Ca2+-free medium or 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, suggesting that it resulted from an influx of extracellular Ca2+. The following four mechanisms that could conceivably have been involved were excluded: 1) Ca2+ displacement of intracellular H+ from common binding sites; 2) activation of an acid loader or inhibition of acid extruders; 3) overproduction of CO2 or lactate; and 4) collapse of the mitochondrial membrane potential due to Ca2+ uptake, resulting in inhibition of cytosolic H+ uptake. However, NMDA/KCl-induced acidosis was largely prevented by glycolytic inhibitors (iodoacetate or deoxyglucose in glucose-free medium) or by inhibitors of the Ca2+-ATPase (i.e., Ca2+/H+ exchanger), including La3+, orthovanadate, eosin B, or an extracellular pH of 8.5. Our results therefore suggest that Ca2+-ATPase is involved in NMDA-induced intracellular acidosis in granule cells. We also provide new evidence that NMDA-evoked intracellular acidosis probably serves as a negative feedback signal, probably with the acidification itself inhibiting the NMDA-induced [Ca2+](i) increase.
Persistent Identifierhttp://hdl.handle.net/10722/171660
ISSN
2015 Impact Factor: 3.395
2015 SCImago Journal Rankings: 1.893
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWu, MLen_US
dc.contributor.authorChen, JHen_US
dc.contributor.authorChen, WHen_US
dc.contributor.authorChen, YUJen_US
dc.contributor.authorChu, KCen_US
dc.date.accessioned2012-10-30T06:16:13Z-
dc.date.available2012-10-30T06:16:13Z-
dc.date.issued1999en_US
dc.identifier.citationAmerican Journal Of Physiology - Cell Physiology, 1999, v. 277 n. 4 46-4, p. C717-C727en_US
dc.identifier.issn0363-6143en_US
dc.identifier.urihttp://hdl.handle.net/10722/171660-
dc.description.abstractThe mechanism involved in N-methyl-D-glucamine (NMDA)-induced Ca2+dependent intracellular acidosis is not clear. In this study, we investigated in detail several possible mechanisms using cultured rat cerebellar granule cells and microfluorometry [fura 2-AM or 2',7'-bis(2- carboxyethyl)-5(6)-carboxyfluorescein-AM]. When 100 μM NMDA or 40 mM KCl was added, a marked increase in the intracellular Ca2+ concentration ([Ca2+](i)) and a decrease in the intracellular pH were seen. Acidosis was completely prevented by the use of Ca2+-free medium or 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, suggesting that it resulted from an influx of extracellular Ca2+. The following four mechanisms that could conceivably have been involved were excluded: 1) Ca2+ displacement of intracellular H+ from common binding sites; 2) activation of an acid loader or inhibition of acid extruders; 3) overproduction of CO2 or lactate; and 4) collapse of the mitochondrial membrane potential due to Ca2+ uptake, resulting in inhibition of cytosolic H+ uptake. However, NMDA/KCl-induced acidosis was largely prevented by glycolytic inhibitors (iodoacetate or deoxyglucose in glucose-free medium) or by inhibitors of the Ca2+-ATPase (i.e., Ca2+/H+ exchanger), including La3+, orthovanadate, eosin B, or an extracellular pH of 8.5. Our results therefore suggest that Ca2+-ATPase is involved in NMDA-induced intracellular acidosis in granule cells. We also provide new evidence that NMDA-evoked intracellular acidosis probably serves as a negative feedback signal, probably with the acidification itself inhibiting the NMDA-induced [Ca2+](i) increase.en_US
dc.languageengen_US
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpcell.physiology.org/en_US
dc.relation.ispartofAmerican Journal of Physiology - Cell Physiologyen_US
dc.subject.meshAcidosis - Chemically Induceden_US
dc.subject.meshAcids - Metabolismen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBinding Sitesen_US
dc.subject.meshCalcium - Metabolismen_US
dc.subject.meshCalcium-Transporting Atpases - Physiologyen_US
dc.subject.meshCarbon Dioxide - Metabolismen_US
dc.subject.meshHydrogen - Metabolismen_US
dc.subject.meshHydrogen-Ion Concentration - Drug Effectsen_US
dc.subject.meshIntracellular Membranes - Metabolismen_US
dc.subject.meshMitochondria - Metabolismen_US
dc.subject.meshN-Methylaspartate - Pharmacologyen_US
dc.subject.meshNeurons - Metabolismen_US
dc.subject.meshOsmolar Concentrationen_US
dc.subject.meshPotassium Chloride - Pharmacologyen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Wistaren_US
dc.titleNovel role of the Ca2+-ATPase in NMDA-induced intracellular acidificationen_US
dc.typeArticleen_US
dc.identifier.emailChen, JH:jhlchen@hku.hken_US
dc.identifier.authorityChen, JH=rp01518en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid10516102-
dc.identifier.scopuseid_2-s2.0-0032696311en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032696311&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume277en_US
dc.identifier.issue4 46-4en_US
dc.identifier.spageC717en_US
dc.identifier.epageC727en_US
dc.identifier.isiWOS:000083919100015-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridWu, ML=22954838100en_US
dc.identifier.scopusauthoridChen, JH=7501878156en_US
dc.identifier.scopusauthoridChen, WH=37162606600en_US
dc.identifier.scopusauthoridChen, YUJ=21333700200en_US
dc.identifier.scopusauthoridChu, KC=7402453598en_US

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