Abstract : Quick cytosolic calcium clearance is essential for the effective modulation of various cellular fun
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Abstract : Quick cytosolic calcium clearance is essential for the effective modulation of various cellular functions. An excess of cytosolic calcium after influx is largely removed via ATP-dependent mechanisms located in the plasma membrane and the endoplasmic reticulum. Therefore calcium clearance depends critically on the adequate supply of ATP which may come from either glycolysis or mitochondria or both. However it presently remains unknown the degree to which individual ATP generating pathways - glycolysis and mitochondria power ATP-dependent calcium as well as other vital ion clearance mechanisms in neurons. In this study we explored the relationship between the energy generating pathways and ion clearance mechanisms in neurons by characterizing the effects of glycolytic and mitochondrial inhibitors of ATP synthesis on calcium clearance kinetics in the soma dendrites and spines. Stimulation of cultured cerebellar granule cells by brief pulses of 60mM potassium ACSF and electrical stimulation of purkinje cells in acutely prepared slices led to a transient calcium influx whose clearance was largely mediated by the plasma membrane Ca(2+)-ATPase pump. Inhibition of glycolysis by deoxyglucose or iodoacetic acid resulted in a marked slowing in calcium clearance in the soma dendrites and spines with the spines affected the most. However inhibition of the mitochondrial citric acid cycle with fluoroacetate and arsenite or mitochondrial ATP synthase with oligomycin did not produce any immediate effects on calcium clearance kinetics in any of those neuronal regions. Although cytosolic calcium clearance was not affected by the inhibition of mitochondria the magnitude of the calcium clearance delay induced by glycolytic inhibitors in different neuronal compartments was related to their mitochondrial density. Conversely the endoplasmic reticulum Ca(2+)-ATPase pump activity is fuelled by both glycolytic and mitochondrial ATP as evidenced by a minimal change in the endoplasmic reticulum calcium contents in cells treated with either deoxyglucose supplemented with lactate or arsenite. Taken together these data suggest that calcium clearance in cerebellar granule and purkinje cells relies on the plasma membrane Ca(2+)-ATPase and is powered by glycolysis.2010 Elsevier Ltd. All rights reserved.PMID 20510449 PubMed - indexed for MEDLINEPMCID PMC2900537 Available on 2011/6/1Publication Types MeSH Terms Substances Grant SupportPublication Types Research Support N.I.H. ExtramuralMeSH TermsAdenosine Triphosphate/biosynthesisAnimalsArsenites/pharmacologyCalcium/metabolism*Calcium-Transporting ATPases/metabolismCells CulturedCerebellum/cytologyCerebellum/metabolism*Citric Acid Cycle/drug effectsEndoplasmic Reticulum/metabolismEnergy Metabolism*GlycolysisLactic Acid/pharmacologyMiceMice Inbred C57BLMitochondria/enzymologyMitochondria/metabolismMitochondrial Proton-Translocating ATPases/metabolismNeurons/metabolism*Purkinje Cells/metabolismSubstancesArsenitesarseniteLactic AcidAdenosine TriphosphateCalciumMitochondrial Proton-Translocating ATPasesCalcium-Transporting ATPasesGrant SupportNS13742-30/NS/NINDS NIH HHS/United StatesLinkOut - more resourcesFull Text SourcesElsevier ScienceEBSCOOhioLINK Electronic Journal CenterSwets Information ServicesMolecular Biology DatabasesCALCIUM COMPOUNDS - HSDBLACTIC ACID - HSDBCALCIUM ELEMENTAL - HSDB Supplemental Content Related citations The role of mitochondria in the regulation of calcium influx into Jurkat cells. Eur J Biochem. 2000 The role of mitochondria in the regulation of calcium influx into Jurkat cells.Makowska A Zablocki K Duszynski J. Eur J Biochem. 2000 Feb 267(3)877-84. Acute glutathione depletion restricts mitochondrial ATP export in cerebellar granule neurons. J Biol Chem. 2005 Acute glutathione depletion restricts mitochondrial ATP export in cerebellar granule neurons.Vesce S Jekabsons MB Johnson-Cadwell LI Nicholls DG. J Biol Chem. 2005 Nov 18 280(46)38720-8. Epub 2005 Sep 19. Fatty acid ethyl esters cause pancreatic calcium toxicity via inositol trisphosphate receptors and loss of ATP synthesis. Gastroenterology. 2006 Fatty acid ethyl esters cause pancreatic calcium toxicity via inositol trisphosphate receptors and loss of ATP synthesis.Criddle DN Murphy J Fistetto G Barrow S Tepikin AV Neoptolemos JP Sutton R Petersen OH. Gastroenterology. 2006 Mar 130(3)781-93. Review Regulation of endoplasmic reticulum-Ca-ATPase by glycolysis in eukaryotic cells. Miner Electrolyte Metab. 1996 Review Regulation of endoplasmic reticulum-Ca-ATPase by glycolysis in eukaryotic cells.Martínez-Zaguilán R Wesson DE. Miner Electrolyte Metab. 1996 22(5-6)318-35. Review Modulating Ca2+ clearance from neurons. Front Biosci. 2002 Review Modulating Ca2+ clearance from neurons.Thayer SA Usachev YM Pottorf WJ. Front Biosci. 2002 May 1 7d1255-79. Epub 2002 May 1. See reviews... See all... All links from this record Related Citations Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant with the “linked from” citation displayed first. Compound (MeSH Keyword) PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles. Substance (MeSH Keyword) PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles. Recent activity Clear Turn Off Turn On Calcium clearance and its energy requirements in cerebellar neurons. Calcium clearance and its energy requirements in cerebellar neurons.Cell Calcium. 2010 Jun 47(6)507-13. Epub 2010 May 26 . PubMed Your browsing activity is empty. Activity recording is turned off. Turn recording back on See more... 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