PMID- 20403073
OWN - NLM
STAT- MEDLINE
DCOM- 20100719
LR  - 20151119
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 114
IP  - 1
DP  - 2010 Jul
TI  - Reduced blockade by extracellular Mg(2+) is permissive to NMDA receptor 
      activation in cerebellar granule neurons that model a migratory phenotype.
PG  - 191-202
LID - 10.1111/j.1471-4159.2010.06746.x [doi]
AB  - NMDA receptors (NMDAR) contribute to neuronal development throughout the CNS. 
      However, their mode(s) of activation preceding synaptic maturation is unclear, as 
      they are not co-localized with 
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPARs) which 
      normally provide sufficient depolarization to relieve voltage-dependent blockade 
      by Mg(2+). We used cerebellar granule neurons (CGNs) cultured at a 
      near-physiological KCl concentration to examine maturation-dependent changes in 
      NMDAR responses. In contrast, most studies use KCl-supplemented medium to promote 
      survival. At 2-4 days in vitro CGNs: (i) express developmental markers resembling 
      the in vivo migratory phenotype; (ii) maintain a basal amount of calcium 
      responsive element-binding protein phosphorylation that requires NMDARs and 
      calcium/calmodulin-dependent kinases, but not AMPARs; (iii) exhibit NMDA-mediated 
      Ca(2+) influx not effectively blocked by ambient Mg(2+) (0.75 mM) or AMPARs; (iv) 
      maintain a more depolarized resting membrane potential and increased resistance 
      compared to synaptically-connected CGNs. Moreover, migrating CGNs in explant 
      cultures demonstrate NMDA-mediated Ca(2+) influx not effectively blocked by 0.75 
      mM Mg(2+), and NMDAR but not AMPAR antagonists slow migration. These data suggest 
      the biophysical properties of immature CGNs render NMDARs less sensitive to 
      Mg(2+) blockade, enhancing the likelihood of activation in the absence of AMPAR 
      depolarization.
FAU - Gerber, Adam M
AU  - Gerber AM
AD  - Department of Neuroscience and Physiology, SUNY Upstate Medical University, 
      Syracuse, New York 13210, USA.
FAU - Beaman-Hall, Carol M
AU  - Beaman-Hall CM
FAU - Mathur, Anjili
AU  - Mathur A
FAU - Vallano, Mary Lou
AU  - Vallano ML
LA  - eng
GR  - DA022368/DA/NIDA NIH HHS/United States
GR  - NS040582/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100409
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Biomarkers)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - I38ZP9992A (Magnesium)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Biomarkers/metabolism
MH  - Calcium/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinases/physiology
MH  - Cell Movement
MH  - Cells, Cultured
MH  - Cerebellum/cytology/*metabolism
MH  - Cyclic AMP Response Element-Binding Protein/physiology
MH  - Extracellular Space/*metabolism
MH  - Magnesium/*metabolism
MH  - Membrane Potentials
MH  - Neurons/*metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Receptors, AMPA/antagonists & inhibitors/physiology
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*physiology
MH  - Signal Transduction
MH  - Synapses/physiology
EDAT- 2010/04/21 06:00
MHDA- 2010/07/20 06:00
CRDT- 2010/04/21 06:00
PHST- 2010/04/21 06:00 [entrez]
PHST- 2010/04/21 06:00 [pubmed]
PHST- 2010/07/20 06:00 [medline]
AID - JNC6746 [pii]
AID - 10.1111/j.1471-4159.2010.06746.x [doi]
PST - ppublish
SO  - J Neurochem. 2010 Jul;114(1):191-202. doi: 10.1111/j.1471-4159.2010.06746.x. Epub 
      2010 Apr 9.