Muscarinic M1, M3, Nicotinic,GABAA and GABAB Receptor ...

implicated in the generation of epilepsy, since an imbalance between excitation
and inhibition produced by a decrease in GABAergic and/or an increase in
glutamatergic transmission has been associated with the generation of this
pathological condition, both in animal models and in humans (Bradford, 1995).
There is an extensive literature showing that seizures can be provoked by blocking
GABA synthesis with 3-mercaptoproprionic acid (MPA) in vivo (Mares et al.,
1993). These studies were demonstrating the involvement of GABA in the
prevention of the over stimulation of neuronal networks.
Glutamate plays an important role in seizure initiation and spread exerting
action not only on ionotropic, but also on metabotropic receptors (Chapman,
1999). Previous reports from our laboratory showed increased glutamate toxicity
in cerebral cortex and cerebellum of hypoglycemic and diabetic rats (Joseph et al.,
2007, 2008). Inhibitory inter-neurons that make use of GABA as their
neurotransmitter are found throughout the brain, but in any region they comprise a
wide range of morphological and functional types that participate in different
circuits with principal neurons. Through the mechanism of recurrent inhibitory
feedback, GABAergic interneurons in the neurons terminate local sustained burst
firing and, through inhibitory surround, limit the lateral spread of seizure activity.
Precise GABAergic synaptic signaling is critical to the accurate transmission of
information within neural circuits and even slight disruptions can produce
hypersynchronous activity (Chagnac-Amitai & Connors, 1989). Moreover,
changes in ambient GABA can alter tonic inhibition and thus the overall synaptic
tone of a brain region (Farrant & Nusser, 2005).
The mechanisms of GABA synthesis and degradation are well understood.
Glutamate is decarboxylated to GABA via glutamic acid decarboxylase (GAD).
GABA that is released into the synaptic cleft, is transported in to both astrocytes
and interneurons through specific transporters. Transported GABA can be
repackaged for subsequent release in interneuronal terminals while astrocytic
GABA is usually metabolized via GABA-transaminase (GABA-T). These
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