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Epilepsy and GABA

Epilepsy and GABA

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Published by ogangurel
Epilepsy and GABA
Epilepsy and GABA

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Published by: ogangurel on Nov 11, 2008
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02/01/2013

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Epilepsy and GABA
Ogan Gurel, CC4
Neurosciences Journal Club
5 October 1995
During MJ, Ryder KM and Spencer DD, \u201cHippocampal GABA transporter function
in temporal\u00adlobe epilepsy,\u201dNat u re, Vol376, 13 July 1995, pp. 174\u00ad177.
SummaryStudied in vivo extracellular GABA levels in hippocampi from temporal lobe epilepsy
patients as well as in amygdala\u00adkindled rats.

Eight patients were studied using implanted microdialysis probes to inject potassium, calcium and glutamate and analyze the effects on extracellular GABA levels.

Likewise, amygdala\u00adkindled rats (an animal\u00admodel of human epilepsy) were similarly studied; additionally, in the rat experiments injections of the specific GABA\u00ad transporter inhibitor nipecotic acid were also assessed both in terms of effects on GABA levels as well as in quantitating the numbers of GABA transporters.

Fig 1
GABA release in the human
hippocampus
Used microdialysis to
study
the
two
types
of
GABA
release:
local
and
generalized.
Epileptogenic hippocampi showed a

relative increase in K+ stimulated, local, vesicular GABA release but showed

a
relative
decrease

in glutamate stimulated, generalized, transport\u00admediated GABA release.

Comment
Numbers are low, but p\u00ad
values
significant.

Technically speaking, microdialysis technically only

analyzes
free

extracellular GABA and may not be representative of

levels
within
the
synaptic
cleft.
Fig 2
GABA release in the rat
hippocampus
Figureb shows the
same results in rats.

In addition, the GABA\u00adtransporter inhibitor nipecotic acid abolished the glutamate\u00admediated increase in extracellular GABA arguing that GABA transport is involved in generalized GABA release.

Comment
It would have been interesting to study the effects on nipecotic acid on the potassium\u00ad
mediated release.
Table 1
3H\u00adNipecotic acid binding in rat hippocampus

Scatchard analysis shows an unchanged Kd but a decreased Bmax in amygdala kindled rats arguing for a quantitative reduction (non\u00ad competitive inhibition model) in the number GABA transporters in \u201cepileptic\u201d rats.

Comment
Intact rat hippocampus, assessment of nonspecific binding, and careful analysis make this
an intriguing and useful result.

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