Expression of Ca(2+)-permeable AMPA receptor channels primes cell death in transient forebrain ischemia.
CA1 pyramidal neurons degenerate after transient global ischemia, whereas neurons in other regions of the hippocampus remain intact. A step in this selective injury is Ca(2+) and/or Zn(2+) entry through Ca(2+)-permeable AMPA receptor channels; reducing Ca(2+) permeability of AMPA receptors via expression of Ca(2+)-impermeable GluR2(R) channels or activation of CRE transcription in the hippocampus of adult rats in vivo using shutoff-deficient pSFV-based vectors rescues vulnerable CA1 pyramidal neurons from forebrain ischemic injury. Conversely, the induction of Ca(2+) and/or Zn(2+) influx through AMPA receptors by expressing functional Ca(2+)-permeable GluR2(Q) channels causes the postischemic degeneration of hippocampal granule neurons that otherwise are insensitive to ischemic insult. Thus, the AMPA receptor subunit GluR2 gates entry of Ca(2+) and/or Zn(2+) that leads to cell death following transient forebrain ischemia.
Liu
ShuHong
S
Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary T2N 4N1, Canada.
Lau
Lorraine
L
Wei
JianShe
J
Zhu
DongYa
D
Zou
Shengwei
S
Sun
Hong-Suo
HS
Fu
YangPing
Y
Liu
Fang
F
Lu
YouMing
Y
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020907:Calcium Channels, Q-Type / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics*; D016923:Cell Death / Q000235:genetics; D002463:Cell Membrane Permeability / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D015640:Ion Channel Gating / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016548:Prosencephalon / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding / Q000235:genetics; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
D015220:Calcium Channels; D020907:Calcium Channels, Q-Type; D017362:Cyclic AMP Response Element-Binding Protein; D018091:Receptors, AMPA; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat; D018844:Cyclin-Dependent Kinases; C045073:Cre recombinase; D019426:Integrases; D015032:Zinc; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium