PMID- 22218089
OWN - NLM
STAT- MEDLINE
DCOM- 20120814
LR  - 20240508
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 37
IP  - 6
DP  - 2012 May
TI  - Increased Kv1 channel expression may contribute to decreased sIPSC frequency 
      following chronic inhibition of NR2B-containing NMDAR.
PG  - 1338-56
LID - 10.1038/npp.2011.320 [doi]
AB  - Numerous studies have documented the effects of chronic N-methyl-D-aspartate 
      receptor (NMDAR) blockade on excitatory circuits, but the effects on inhibitory 
      circuitry are not well studied. NR2A- and NR2B-containing NMDARs play 
      differential roles in physiological processes, but the consequences of chronic 
      NR2A- or NR2B-containing NMDAR inhibition on glutamatergic and GABAergic 
      neurotransmission are unknown. We investigated altered GABAergic 
      neurotransmission in dentate granule cells and interneurons following chronic 
      treatment with the NR2B-selective antagonist, Ro25,6981, the NR2A-prefering 
      antagonist, NVP-AAM077, or the non-subunit-selective NMDAR antagonist, D-APV, in 
      organotypic hippocampal slice cultures. Electrophysiological recordings revealed 
      large reductions in spontaneous inhibitory postsynaptic current (sIPSC) frequency 
      in both granule cells and interneurons following chronic Ro25,6981 treatment, 
      which was associated with minimally altered sIPSC amplitude, miniature inhibitory 
      postsynaptic current (mIPSC) frequency, and mIPSC amplitude, suggesting 
      diminished action potential-dependent GABA release. Chronic NVP-AAM077 or D-APV 
      treatment had little effect on these measures. Reduced sIPSC frequency did not 
      arise from downregulated GABA(A)R, altered excitatory or inhibitory drive to 
      interneurons, altered interneuron membrane properties, increased failure rate, 
      decreased action potential-dependent release probability, or mGluR/GABA(B) 
      receptor modulation of GABA release. However, chronic Ro25,6981-mediated 
      reductions in sIPSC frequency were occluded by the K+ channel blockers, 
      dendrotoxin, margatoxin, and agitoxin, but not dendrotoxin-K or XE991. 
      Immunohistochemistry also showed increased Kv1.2, Kv1.3, and Kv1.6 in the dentate 
      molecular layer following chronic Ro25,6981 treatment. Our findings suggest that 
      increased Kv1 channel expression/function contributed to diminished action 
      potential-dependent GABA release following chronic NR2B-containing NMDAR 
      inhibition and that these Kv1 channels may be heteromeric complexes containing 
      Kv1.2, Kv1.3, and Kv1.6.
FAU - He, Shuijin
AU  - He S
AD  - Department of Pharmacology, Uniformed Services University School of Medicine, 
      Bethesda, MD, USA.
FAU - Shao, Li-Rong
AU  - Shao LR
FAU - Rittase, W Bradley
AU  - Rittase WB
FAU - Bausch, Suzanne B
AU  - Bausch SB
LA  - eng
GR  - R01 NS045964/NS/NINDS NIH HHS/United States
GR  - U24 NS050606/NS/NINDS NIH HHS/United States
GR  - NS045964/NS/NINDS NIH HHS/United States
GR  - U24NS050606/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20120104
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (NR2A NMDA receptor)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Potassium Channels)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Shaker Superfamily of Potassium Channels)
RN  - 0 (Sodium Channel Blockers)
RN  - 0 (neurobiotin)
RN  - 4368-28-9 (Tetrodotoxin)
RN  - 6SO6U10H04 (Biotin)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Biophysics
MH  - Biotin/analogs & derivatives/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Electric Stimulation
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Gene Expression Regulation/drug effects/*physiology
MH  - Hippocampus/cytology/drug effects/metabolism
MH  - Inhibitory Postsynaptic Potentials/drug effects/*physiology
MH  - Interneurons/drug effects/physiology
MH  - Organ Culture Techniques
MH  - Patch-Clamp Techniques
MH  - Potassium Channel Blockers/pharmacology
MH  - Potassium Channels/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Shaker Superfamily of Potassium Channels/*metabolism
MH  - Sodium Channel Blockers
MH  - Statistics, Nonparametric
MH  - Tetrodotoxin/pharmacology
PMC - PMC3327840
EDAT- 2012/01/06 06:00
MHDA- 2012/08/15 06:00
PMCR- 2013/05/01
CRDT- 2012/01/06 06:00
PHST- 2012/01/06 06:00 [entrez]
PHST- 2012/01/06 06:00 [pubmed]
PHST- 2012/08/15 06:00 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - npp2011320 [pii]
AID - 10.1038/npp.2011.320 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2012 May;37(6):1338-56. doi: 10.1038/npp.2011.320. Epub 
      2012 Jan 4.