Mitochondrial permeability transition and calcium dynamics in striatal neurons upon intense NMDA receptor activation
Deregulation of the intracellular Ca2+ homeostasis by NMDA receptor activation leads to neuronal cell death. Induction of the mitochondrial permeability transition pore (MPT) by Ca2+ is a critical event in mediating cell death. In this study, we used fluorescent Ca2+ indicators to investigate the ef...
Gespeichert in:
| Veröffentlicht in: | Journal of neurochemistry 2002-02, Vol.80 (3), p.531-538 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 538 |
|---|---|
| container_issue | 3 |
| container_start_page | 531 |
| container_title | Journal of neurochemistry |
| container_volume | 80 |
| creator | Alano, Conrad C. Beutner, Gisela Dirksen, Robert T. Gross, Robert A. Sheu, Shey‐Shing |
| description | Deregulation of the intracellular Ca2+ homeostasis by NMDA receptor activation leads to neuronal cell death. Induction of the mitochondrial permeability transition pore (MPT) by Ca2+ is a critical event in mediating cell death. In this study, we used fluorescent Ca2+ indicators to investigate the effect of high concentrations of NMDA on cytosolic and mitochondrial Ca2+ concentrations ([Ca2+]c and [Ca2+]m, respectively) in cultured striatal neurons. Exposure to NMDA resulted in an immediate, sustained increase in [Ca2+]c followed by a secondary increase in [Ca2+]c. This second increase of [Ca2+]c was prevented by pretreatment with N‐methyl‐valine‐4‐cyclosporin (NMV‐Cys). Exposure of neurons to NMDA also resulted in an increase in [Ca2+]m that was followed by a precipitous decrease in the rhod‐2 signal. This decrease followed the time frame of the secondary increase in [Ca2+]c. Preincubation of the neurons with NMV‐Cys prevented the decrease in rhod‐2 fluorescence. These dynamic changes in the rhod‐2 signal and [Ca2+]m in response to NMDA were confirmed by using confocal microscopy. The presented results indicate that MPT can be detected in living neurons using fluorescent Ca2+ indicators, which would allow the study of the physiological role of MPT in cell death. |
| doi_str_mv | 10.1046/j.0022-3042.2001.00738.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71548337</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71548337</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4768-5a5c0b503800f47590913d9ca10416d90f9911f43fec5a6b26902471b4a9b1f13</originalsourceid><addsrcrecordid>eNqNkU9v2yAYxtHUakm7fYWJS3tzymvwHw47RFn_Ksku2xlhjDUiG7uAu-bbFy_RcmxPgPR74OX3IISBLICw_Ga3ICRNE0pYukgJgXgsaLl4_YTmwApIGGT8DM3_QzN04f0ugjnL4TOaAXCScV7OUdiY0Ks_va2dkS0etOu0rExrwh4HJ603wfQWS1tjJVtlxg7Xeys7ozw2FvsQYyEGrR5dbz0eh0gbG7T1Gm83P5bYaaWH0DssVTAvcrruCzpvZOv11-N6iX7f3f5aPSTrn_ePq-U6UazIyySTmSJVRmhJSMOKjBMOtOZKRgeQ15w0nAM0jDZaZTKv0pyTNH6_YpJX0AC9RNeHewfXP4_aB9EZr3TbSqv70YsCMlZSWrwLQsmisYJGsDyAyvXeO92IwZlOur0AIqZqxE5M1sVkXUzViH_ViNcY_XZ8Y6w6XZ-Cxy4icHUEpI-um2hfGX_iKGNxgjRy3w_cX9Pq_YcHEE_b1bSjbz-QqpM</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>18419073</pqid></control><display><type>article</type><title>Mitochondrial permeability transition and calcium dynamics in striatal neurons upon intense NMDA receptor activation</title><source>MEDLINE</source><source>Wiley Online Library Free Content</source><source>Access via Wiley Online Library</source><source>IngentaConnect Free/Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Free Full-Text Journals in Chemistry</source><creator>Alano, Conrad C. ; Beutner, Gisela ; Dirksen, Robert T. ; Gross, Robert A. ; Sheu, Shey‐Shing</creator><creatorcontrib>Alano, Conrad C. ; Beutner, Gisela ; Dirksen, Robert T. ; Gross, Robert A. ; Sheu, Shey‐Shing</creatorcontrib><description>Deregulation of the intracellular Ca2+ homeostasis by NMDA receptor activation leads to neuronal cell death. Induction of the mitochondrial permeability transition pore (MPT) by Ca2+ is a critical event in mediating cell death. In this study, we used fluorescent Ca2+ indicators to investigate the effect of high concentrations of NMDA on cytosolic and mitochondrial Ca2+ concentrations ([Ca2+]c and [Ca2+]m, respectively) in cultured striatal neurons. Exposure to NMDA resulted in an immediate, sustained increase in [Ca2+]c followed by a secondary increase in [Ca2+]c. This second increase of [Ca2+]c was prevented by pretreatment with N‐methyl‐valine‐4‐cyclosporin (NMV‐Cys). Exposure of neurons to NMDA also resulted in an increase in [Ca2+]m that was followed by a precipitous decrease in the rhod‐2 signal. This decrease followed the time frame of the secondary increase in [Ca2+]c. Preincubation of the neurons with NMV‐Cys prevented the decrease in rhod‐2 fluorescence. These dynamic changes in the rhod‐2 signal and [Ca2+]m in response to NMDA were confirmed by using confocal microscopy. The presented results indicate that MPT can be detected in living neurons using fluorescent Ca2+ indicators, which would allow the study of the physiological role of MPT in cell death.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1046/j.0022-3042.2001.00738.x</identifier><identifier>PMID: 11905998</identifier><identifier>CODEN: JONRA9</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science, Ltd</publisher><subject>Animals ; Biochemistry and metabolism ; Biological and medical sciences ; calcium ; Calcium - metabolism ; cell death ; Cell Death - drug effects ; Cell Death - physiology ; Cells, Cultured ; Central nervous system ; Corpus Striatum - cytology ; Cyclosporine - pharmacology ; Excitatory Amino Acid Agonists - pharmacology ; Fundamental and applied biological sciences. Psychology ; Microscopy, Confocal ; mitochondria ; Mitochondria - metabolism ; N-Methylaspartate - pharmacology ; Neurons - cytology ; Neurons - metabolism ; NMDA ; permeability transition ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate - metabolism ; striatal neurons ; Vertebrates: nervous system and sense organs</subject><ispartof>Journal of neurochemistry, 2002-02, Vol.80 (3), p.531-538</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4768-5a5c0b503800f47590913d9ca10416d90f9911f43fec5a6b26902471b4a9b1f13</citedby><cites>FETCH-LOGICAL-c4768-5a5c0b503800f47590913d9ca10416d90f9911f43fec5a6b26902471b4a9b1f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.0022-3042.2001.00738.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.0022-3042.2001.00738.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13447332$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11905998$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alano, Conrad C.</creatorcontrib><creatorcontrib>Beutner, Gisela</creatorcontrib><creatorcontrib>Dirksen, Robert T.</creatorcontrib><creatorcontrib>Gross, Robert A.</creatorcontrib><creatorcontrib>Sheu, Shey‐Shing</creatorcontrib><title>Mitochondrial permeability transition and calcium dynamics in striatal neurons upon intense NMDA receptor activation</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>Deregulation of the intracellular Ca2+ homeostasis by NMDA receptor activation leads to neuronal cell death. Induction of the mitochondrial permeability transition pore (MPT) by Ca2+ is a critical event in mediating cell death. In this study, we used fluorescent Ca2+ indicators to investigate the effect of high concentrations of NMDA on cytosolic and mitochondrial Ca2+ concentrations ([Ca2+]c and [Ca2+]m, respectively) in cultured striatal neurons. Exposure to NMDA resulted in an immediate, sustained increase in [Ca2+]c followed by a secondary increase in [Ca2+]c. This second increase of [Ca2+]c was prevented by pretreatment with N‐methyl‐valine‐4‐cyclosporin (NMV‐Cys). Exposure of neurons to NMDA also resulted in an increase in [Ca2+]m that was followed by a precipitous decrease in the rhod‐2 signal. This decrease followed the time frame of the secondary increase in [Ca2+]c. Preincubation of the neurons with NMV‐Cys prevented the decrease in rhod‐2 fluorescence. These dynamic changes in the rhod‐2 signal and [Ca2+]m in response to NMDA were confirmed by using confocal microscopy. The presented results indicate that MPT can be detected in living neurons using fluorescent Ca2+ indicators, which would allow the study of the physiological role of MPT in cell death.</description><subject>Animals</subject><subject>Biochemistry and metabolism</subject><subject>Biological and medical sciences</subject><subject>calcium</subject><subject>Calcium - metabolism</subject><subject>cell death</subject><subject>Cell Death - drug effects</subject><subject>Cell Death - physiology</subject><subject>Cells, Cultured</subject><subject>Central nervous system</subject><subject>Corpus Striatum - cytology</subject><subject>Cyclosporine - pharmacology</subject><subject>Excitatory Amino Acid Agonists - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Microscopy, Confocal</subject><subject>mitochondria</subject><subject>Mitochondria - metabolism</subject><subject>N-Methylaspartate - pharmacology</subject><subject>Neurons - cytology</subject><subject>Neurons - metabolism</subject><subject>NMDA</subject><subject>permeability transition</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><subject>striatal neurons</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU9v2yAYxtHUakm7fYWJS3tzymvwHw47RFn_Ksku2xlhjDUiG7uAu-bbFy_RcmxPgPR74OX3IISBLICw_Ga3ICRNE0pYukgJgXgsaLl4_YTmwApIGGT8DM3_QzN04f0ugjnL4TOaAXCScV7OUdiY0Ks_va2dkS0etOu0rExrwh4HJ603wfQWS1tjJVtlxg7Xeys7ozw2FvsQYyEGrR5dbz0eh0gbG7T1Gm83P5bYaaWH0DssVTAvcrruCzpvZOv11-N6iX7f3f5aPSTrn_ePq-U6UazIyySTmSJVRmhJSMOKjBMOtOZKRgeQ15w0nAM0jDZaZTKv0pyTNH6_YpJX0AC9RNeHewfXP4_aB9EZr3TbSqv70YsCMlZSWrwLQsmisYJGsDyAyvXeO92IwZlOur0AIqZqxE5M1sVkXUzViH_ViNcY_XZ8Y6w6XZ-Cxy4icHUEpI-um2hfGX_iKGNxgjRy3w_cX9Pq_YcHEE_b1bSjbz-QqpM</recordid><startdate>200202</startdate><enddate>200202</enddate><creator>Alano, Conrad C.</creator><creator>Beutner, Gisela</creator><creator>Dirksen, Robert T.</creator><creator>Gross, Robert A.</creator><creator>Sheu, Shey‐Shing</creator><general>Blackwell Science, Ltd</general><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>200202</creationdate><title>Mitochondrial permeability transition and calcium dynamics in striatal neurons upon intense NMDA receptor activation</title><author>Alano, Conrad C. ; Beutner, Gisela ; Dirksen, Robert T. ; Gross, Robert A. ; Sheu, Shey‐Shing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4768-5a5c0b503800f47590913d9ca10416d90f9911f43fec5a6b26902471b4a9b1f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Biochemistry and metabolism</topic><topic>Biological and medical sciences</topic><topic>calcium</topic><topic>Calcium - metabolism</topic><topic>cell death</topic><topic>Cell Death - drug effects</topic><topic>Cell Death - physiology</topic><topic>Cells, Cultured</topic><topic>Central nervous system</topic><topic>Corpus Striatum - cytology</topic><topic>Cyclosporine - pharmacology</topic><topic>Excitatory Amino Acid Agonists - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Microscopy, Confocal</topic><topic>mitochondria</topic><topic>Mitochondria - metabolism</topic><topic>N-Methylaspartate - pharmacology</topic><topic>Neurons - cytology</topic><topic>Neurons - metabolism</topic><topic>NMDA</topic><topic>permeability transition</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, N-Methyl-D-Aspartate - metabolism</topic><topic>striatal neurons</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alano, Conrad C.</creatorcontrib><creatorcontrib>Beutner, Gisela</creatorcontrib><creatorcontrib>Dirksen, Robert T.</creatorcontrib><creatorcontrib>Gross, Robert A.</creatorcontrib><creatorcontrib>Sheu, Shey‐Shing</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alano, Conrad C.</au><au>Beutner, Gisela</au><au>Dirksen, Robert T.</au><au>Gross, Robert A.</au><au>Sheu, Shey‐Shing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mitochondrial permeability transition and calcium dynamics in striatal neurons upon intense NMDA receptor activation</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>2002-02</date><risdate>2002</risdate><volume>80</volume><issue>3</issue><spage>531</spage><epage>538</epage><pages>531-538</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><coden>JONRA9</coden><abstract>Deregulation of the intracellular Ca2+ homeostasis by NMDA receptor activation leads to neuronal cell death. Induction of the mitochondrial permeability transition pore (MPT) by Ca2+ is a critical event in mediating cell death. In this study, we used fluorescent Ca2+ indicators to investigate the effect of high concentrations of NMDA on cytosolic and mitochondrial Ca2+ concentrations ([Ca2+]c and [Ca2+]m, respectively) in cultured striatal neurons. Exposure to NMDA resulted in an immediate, sustained increase in [Ca2+]c followed by a secondary increase in [Ca2+]c. This second increase of [Ca2+]c was prevented by pretreatment with N‐methyl‐valine‐4‐cyclosporin (NMV‐Cys). Exposure of neurons to NMDA also resulted in an increase in [Ca2+]m that was followed by a precipitous decrease in the rhod‐2 signal. This decrease followed the time frame of the secondary increase in [Ca2+]c. Preincubation of the neurons with NMV‐Cys prevented the decrease in rhod‐2 fluorescence. These dynamic changes in the rhod‐2 signal and [Ca2+]m in response to NMDA were confirmed by using confocal microscopy. The presented results indicate that MPT can be detected in living neurons using fluorescent Ca2+ indicators, which would allow the study of the physiological role of MPT in cell death.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science, Ltd</pub><pmid>11905998</pmid><doi>10.1046/j.0022-3042.2001.00738.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-3042 |
| ispartof | Journal of neurochemistry, 2002-02, Vol.80 (3), p.531-538 |
| issn | 0022-3042 1471-4159 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71548337 |
| source | MEDLINE; Wiley Online Library Free Content; Access via Wiley Online Library; IngentaConnect Free/Open Access Journals; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Animals Biochemistry and metabolism Biological and medical sciences calcium Calcium - metabolism cell death Cell Death - drug effects Cell Death - physiology Cells, Cultured Central nervous system Corpus Striatum - cytology Cyclosporine - pharmacology Excitatory Amino Acid Agonists - pharmacology Fundamental and applied biological sciences. Psychology Microscopy, Confocal mitochondria Mitochondria - metabolism N-Methylaspartate - pharmacology Neurons - cytology Neurons - metabolism NMDA permeability transition Rats Rats, Sprague-Dawley Receptors, N-Methyl-D-Aspartate - metabolism striatal neurons Vertebrates: nervous system and sense organs |
| title | Mitochondrial permeability transition and calcium dynamics in striatal neurons upon intense NMDA receptor activation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T22%3A23%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mitochondrial%20permeability%20transition%20and%20calcium%20dynamics%20in%20striatal%20neurons%20upon%20intense%20NMDA%20receptor%20activation&rft.jtitle=Journal%20of%20neurochemistry&rft.au=Alano,%20Conrad%20C.&rft.date=2002-02&rft.volume=80&rft.issue=3&rft.spage=531&rft.epage=538&rft.pages=531-538&rft.issn=0022-3042&rft.eissn=1471-4159&rft.coden=JONRA9&rft_id=info:doi/10.1046/j.0022-3042.2001.00738.x&rft_dat=%3Cproquest_cross%3E71548337%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=18419073&rft_id=info:pmid/11905998&rfr_iscdi=true |