PMID- 17490438
OWN - NLM
STAT- MEDLINE
DCOM- 20071019
LR  - 20180308
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 102
IP  - 6
DP  - 2007 Sep
TI  - AMPA-mediated excitotoxicity in oligodendrocytes: role for Na(+)-K(+)-Cl(-) 
      co-transport and reversal of Na(+)/Ca(2+) exchanger.
PG  - 1783-1795
LID - 10.1111/j.1471-4159.2007.04638.x [doi]
AB  - We investigated the role of Na(+)-K(+)-Cl(-) co-transporter isoform 1 (NKCC1) and 
      reversal of Na(+)/Ca(2+) exchanger (NCX(rev)) in glutamate-mediated 
      excitotoxicity in oligodendrocytes obtained from rat spinal cords (postnatal day 
      6-8). An immunocytochemical characterization showed that these cultures express 
      NKCC1 and Na(+)/Ca(2+) exchanger isoforms 1, 2, and 3 (NCX1, NCX2, NCX3). 
      Exposing the cultures to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 
      (AMPA) plus cyclothiazide (CTZ) led to a transient rise in intracellular (), 
      which was followed by a sustained overload, NKCC1 phosphorylation, and a 
      NKCC1-mediated Na(+) influx. In the presence of a specific AMPA receptor 
      inhibitor 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX), the AMPA/CTZ failed to 
      elicit any changes in . The AMPA/CTZ-induced sustained rise led to mitochondrial 
      Ca(2+) accumulation, release of cytochrome c from mitochondria, and cell death. 
      The AMPA/CTZ-elicited increase, mitochondrial damage, and cell death were 
      significantly reduced by inhibiting NKCC1 or NCX(rev). These data suggest that in 
      cultured oligodendrocytes, activation of AMPA receptors leads to NKCC1 
      phosphorylation that enhances NKCC1-mediated Na(+) influx. The latter triggers 
      NCX(rev) and NCX(rev)-mediated overload and compromises mitochondrial function 
      and cellular viability.
FAU - Chen, Hai
AU  - Chen H
AD  - Neuroscience Training Program, University of Wisconsin Medical School, Madison, 
      Wisconsin, USADepartments of Neurosurgery, University of Wisconsin Medical 
      School, Madison, Wisconsin, USAPhysiology, University of Wisconsin Medical 
      School, Madison, Wisconsin, USAGraduate School of Pharmaceutical Sciences, Osaka 
      University, Osaka, JapanDepartments of Psychiatry and Pharmacology, University of 
      Illinois at Chicago, Illinois, USA.
FAU - Kintner, Douglas B
AU  - Kintner DB
AD  - Neuroscience Training Program, University of Wisconsin Medical School, Madison, 
      Wisconsin, USADepartments of Neurosurgery, University of Wisconsin Medical 
      School, Madison, Wisconsin, USAPhysiology, University of Wisconsin Medical 
      School, Madison, Wisconsin, USAGraduate School of Pharmaceutical Sciences, Osaka 
      University, Osaka, JapanDepartments of Psychiatry and Pharmacology, University of 
      Illinois at Chicago, Illinois, USA.
FAU - Jones, Mathew
AU  - Jones M
AD  - Neuroscience Training Program, University of Wisconsin Medical School, Madison, 
      Wisconsin, USADepartments of Neurosurgery, University of Wisconsin Medical 
      School, Madison, Wisconsin, USAPhysiology, University of Wisconsin Medical 
      School, Madison, Wisconsin, USAGraduate School of Pharmaceutical Sciences, Osaka 
      University, Osaka, JapanDepartments of Psychiatry and Pharmacology, University of 
      Illinois at Chicago, Illinois, USA.
FAU - Matsuda, Toshio
AU  - Matsuda T
AD  - Neuroscience Training Program, University of Wisconsin Medical School, Madison, 
      Wisconsin, USADepartments of Neurosurgery, University of Wisconsin Medical 
      School, Madison, Wisconsin, USAPhysiology, University of Wisconsin Medical 
      School, Madison, Wisconsin, USAGraduate School of Pharmaceutical Sciences, Osaka 
      University, Osaka, JapanDepartments of Psychiatry and Pharmacology, University of 
      Illinois at Chicago, Illinois, USA.
FAU - Baba, Akemichi
AU  - Baba A
AD  - Neuroscience Training Program, University of Wisconsin Medical School, Madison, 
      Wisconsin, USADepartments of Neurosurgery, University of Wisconsin Medical 
      School, Madison, Wisconsin, USAPhysiology, University of Wisconsin Medical 
      School, Madison, Wisconsin, USAGraduate School of Pharmaceutical Sciences, Osaka 
      University, Osaka, JapanDepartments of Psychiatry and Pharmacology, University of 
      Illinois at Chicago, Illinois, USA.
FAU - Kiedrowski, Lech
AU  - Kiedrowski L
AD  - Neuroscience Training Program, University of Wisconsin Medical School, Madison, 
      Wisconsin, USADepartments of Neurosurgery, University of Wisconsin Medical 
      School, Madison, Wisconsin, USAPhysiology, University of Wisconsin Medical 
      School, Madison, Wisconsin, USAGraduate School of Pharmaceutical Sciences, Osaka 
      University, Osaka, JapanDepartments of Psychiatry and Pharmacology, University of 
      Illinois at Chicago, Illinois, USA.
FAU - Sun, Dandan
AU  - Sun D
AD  - Neuroscience Training Program, University of Wisconsin Medical School, Madison, 
      Wisconsin, USADepartments of Neurosurgery, University of Wisconsin Medical 
      School, Madison, Wisconsin, USAPhysiology, University of Wisconsin Medical 
      School, Madison, Wisconsin, USAGraduate School of Pharmaceutical Sciences, Osaka 
      University, Osaka, JapanDepartments of Psychiatry and Pharmacology, University of 
      Illinois at Chicago, Illinois, USA.
LA  - eng
GR  - R01NS048216/NS/NINDS NIH HHS/United States
GR  - R01NS38118/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070508
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Benzothiadiazines)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Neurotoxins)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Slc12a2 protein, rat)
RN  - 0 (Slc8a2 protein, rat)
RN  - 0 (Slc8a3 protein, rat)
RN  - 0 (Sodium-Calcium Exchanger)
RN  - 0 (Sodium-Potassium-Chloride Symporters)
RN  - 0 (Solute Carrier Family 12, Member 2)
RN  - 0 (sodium-calcium exchanger 1)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid)
RN  - 9NEZ333N27 (Sodium)
RN  - P71U09G5BW (cyclothiazide)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Antihypertensive Agents/pharmacology
MH  - Benzothiadiazines/pharmacology
MH  - Calcium/metabolism
MH  - Cell Death/drug effects/physiology
MH  - Cells, Cultured
MH  - Central Nervous System/*metabolism
MH  - Excitatory Amino Acid Agonists/pharmacology
MH  - Glutamic Acid/metabolism/toxicity
MH  - Membrane Transport Proteins/drug effects/metabolism
MH  - Mitochondria/drug effects/metabolism
MH  - Neurotoxins/*metabolism/toxicity
MH  - Oligodendroglia/drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, AMPA/antagonists & inhibitors/drug effects/*metabolism
MH  - Sodium/metabolism
MH  - Sodium-Calcium Exchanger/drug effects/*metabolism
MH  - Sodium-Potassium-Chloride Symporters/drug effects/*metabolism
MH  - Solute Carrier Family 12, Member 2
MH  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology
EDAT- 2007/05/11 09:00
MHDA- 2007/10/20 09:00
CRDT- 2007/05/11 09:00
PHST- 2007/05/11 09:00 [pubmed]
PHST- 2007/10/20 09:00 [medline]
PHST- 2007/05/11 09:00 [entrez]
AID - 10.1111/j.1471-4159.2007.04638.x [doi]
PST - ppublish
SO  - J Neurochem. 2007 Sep;102(6):1783-1795. doi: 10.1111/j.1471-4159.2007.04638.x. 
      Epub 2007 May 8.