PMID- 19453710
OWN - NLM
STAT- MEDLINE
DCOM- 20101015
LR  - 20131121
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Linking)
VI  - 50
IP  - 7
DP  - 2009 Jul
TI  - Impaired function of GABA(B) receptors in tissues from pharmacoresistant epilepsy 
      patients.
PG  - 1697-716
LID - 10.1111/j.1528-1167.2009.02094.x [doi]
AB  - PURPOSE: Effects of pre- and postsynaptic gamma-aminobutyric acid B (GABA(B)) 
      receptor activation were characterized in human tissue from epilepsy surgery. 
      METHODS: Slices of human cortical tissue were investigated in a submerged-type 
      chamber with intracellular recordings in layers II/III. Parallel experiments were 
      performed in rat neocortical slices with identical methods. Synaptic responses 
      were elicited with single or paired stimulations of incrementing intervals. 
      RESULTS: Neurons in human epileptogenic tissue exhibited usually small inhibitory 
      postsynaptic potentials (IPSP) mediated by GABA(B) receptor, verified by the 
      sensitivity to the selective antagonist CGP 55845A. The IPSP(B) conductance 
      averaged 5.8 nS in neurons from epileptogenic tissues and 15.9 nS in neurons from 
      nonepileptogenic tissues (p < 0.0001). Application of baclofen caused small 
      conductance increases in human neurons, which were linearly related to IPSP(B) 
      conductances. Paired-pulse stimulation revealed constant synaptic responses in 
      human temporal lobe epilepsy (TLE) slices at all interstimulus intervals (ISIs). 
      Pharmacologically isolated IPSP(A) in the human tissue exhibited a small 
      paired-pulse depression (average 10% at 500 ms ISI). Bicuculline-induced 
      paroxysmal depolarization shifts (PDSs) were transiently depressed by 24% in 
      human TLE tissue; and by 74% in rat neocortical slices (200 ms ISI; p = 0.015). 
      The depressions of bicuculline-induced PDSs were antagonized by CGP 55845A in 
      both species. Staining for GABA(B) receptors revealed significantly smaller 
      numbers of immunopositive dots in human epileptogenic neurons versus human 
      control neurons. DISCUSSION: The small IPSP(B), baclofen-conductances, and 
      paired-pulse depression of PDSs and IPSPs in human TLE tissue indicate a reduced 
      density of post- and presynaptic GABA(B) receptors. The reduced efficacy of 
      presynaptic GABA(B) receptors facilitates the occurrence of repetitive synaptic 
      activity.
FAU - Teichgraber, Laura A
AU  - Teichgraber LA
AD  - Center for Anatomy, Institute for Cell Biology and Neurobiology, 
      Charite-Universitatsmedizin Berlin, Berlin, Germany.
FAU - Lehmann, Thomas-Nicolas
AU  - Lehmann TN
FAU - Meencke, Heinz-Joachim
AU  - Meencke HJ
FAU - Weiss, Torsten
AU  - Weiss T
FAU - Nitsch, Robert
AU  - Nitsch R
FAU - Deisz, Rudolf A
AU  - Deisz RA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090527
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Anticonvulsants)
RN  - 0 (GABA-B Receptor Antagonists)
RN  - 0 (Phosphinic Acids)
RN  - 0 (Propanolamines)
RN  - 0 (Receptors, GABA-B)
RN  - 148056-42-2 (CGP 55845A)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - H789N3FKE8 (Baclofen)
RN  - Y37615DVKC (Bicuculline)
SB  - IM
MH  - Animals
MH  - Anticonvulsants/pharmacology/*therapeutic use
MH  - Baclofen/pharmacology
MH  - Bicuculline/pharmacology
MH  - Cerebral Cortex/drug effects/physiopathology
MH  - Drug Resistance
MH  - Epilepsy/*drug therapy/*physiopathology
MH  - Epilepsy, Temporal Lobe/drug therapy/physiopathology
MH  - Excitatory Postsynaptic Potentials/drug effects/physiology
MH  - GABA-B Receptor Antagonists
MH  - Humans
MH  - Immunohistochemistry
MH  - Mice
MH  - Neurons/*drug effects/physiology
MH  - Phosphinic Acids/pharmacology
MH  - Propanolamines/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, GABA-B/*drug effects/physiology
MH  - Synaptic Transmission/drug effects/physiology
MH  - gamma-Aminobutyric Acid/pharmacology/physiology
EDAT- 2009/05/21 09:00
MHDA- 2010/10/16 06:00
CRDT- 2009/05/21 09:00
PHST- 2009/05/21 09:00 [entrez]
PHST- 2009/05/21 09:00 [pubmed]
PHST- 2010/10/16 06:00 [medline]
AID - EPI2094 [pii]
AID - 10.1111/j.1528-1167.2009.02094.x [doi]
PST - ppublish
SO  - Epilepsia. 2009 Jul;50(7):1697-716. doi: 10.1111/j.1528-1167.2009.02094.x. Epub 
      2009 May 27.