Extracellular Level of GABA and Glu: In Vivo Microdialysis-HPLC Measurements

Abstract

In spite of several studies showing specific physiological functions of changes in the extracellular level of the major excitatory and inhibitory transmitters, Glu and GABA within the brain ([Glu](EXT), [GABA](EXT)) the exact origin (neuronal vs. astroglial, synaptic vs. extrasynaptic) of Glu and GABA present in dialysate samples is still a matter of debate. For better understanding the significance of in vivo microdialysis data, here we discuss methodological details and problems in addition to regulation of [Glu](EXT) and [GABA](EXT). Changes in [Glu](EXT) and [GABA](EXT) under pathological conditions such as ischemia and epilepsy are also reviewed. Based on recent in vivo microdialysis data we argue that ambient [Glu](EXT) and [GABA](EXT)may have a functional role. It is suggested that specific changes in concentrations of Glu and GABA in dialysate samples together with their alterations independent of neuronal activity indicate the involvement of Glu and GABA in the information processing of the brain as essential signaling molecules of nonsynaptic transmission as well. Since various drugs are able to interfere with extrasynaptic signals in vivo, studying the extracellular cell-to-cell communication of brain cells represents a new aspect to improve drugs modulating Gluergic as well as GABAergic neurotransmission.

Extracellular Glutamate Concentration in Hippocampal Slice

“…We determined that the tonic spatially and temporally averaged concentration of extracellular glutamate in acute hippocampal slices with intact glutamate transport is ϳ25 nM, 100-fold lower than reported previously (Lerma et al, 1986;Baker et al, 2002;Nyitrai et al, 2006). We suggest that this low concentration of extracellular glutamate is controlled by densely expressed glutamate transporters (Garthwaite, 1985;Jabaudon et al, 1999;Danbolt, 2001;.…”

“…Although the thermodynamic coupling of Na ϩ and K ϩ gradients to glutamate transport predicts a lower limit of 2 nM extracellular glutamate (Zerangue and Kavanaugh, 1996), the constant efflux of glutamate results in a higher steady-state ambient concentration in the extracellular space (Sah et al, 1989;Rossi and Slater, 1993;Lauri et al, 2006;Le Meur et al, 2007). Microdialysis studies report an in vivo ambient glutamate concentration as high as 1-4 M (Lerma et al, 1986;Baker et al, 2002;Nyitrai et al, 2006). Given that the EC 50 of the NMDA receptor (NMDAR) for glutamate is ϳ2 M (Patneau and Mayer, 1990), this concentration range would have significant effects on neuronal excitability.…”

A new meaning for “Gin & Tonic”: tonic inhibition as the target for ethanol action in the brain

“…However, to function as receptors capable to detect low concentrations of extrasynaptic GABA, these receptors have to satisfy certain pharmacological criteria. First, they have to have a high affinity for GABA in order to be activated by the low concentration of transmitter in the extracellular space estimated to be in the range of one to a few μM (Kuntz et al, 2004;Nyitrai et al, 2006). Second, they have to be devoid of desensitization, as receptors in the continuing presence of agonist tend to desensitize and spend their time mainly in the closed configuration.…”

Development and Validation of a Specific RP-HPLC Method for the Estimation of γ-Aminobutyric Acid in Rat Brain Tissue Samples Using Benzoyl Chloride Derivatization and PDA Detection

“…The animals treated with acute pentylenetetrazol (80 mg kg −1 i.p. ), a potent convulsant, showed a slight increase in the GABA levels in postmortem brain tissues, which may be due to the blockade of presynaptic GABA receptors mediating an inhibition of GABA release on GABAergic nerve terminals [24,25]. Though the sensitivity of the present method is comparable to or lower than some of the existing reports, the use of electrochemical or fluorescence detector, a high-pressure six-way switching valve, gradient elution, microbore column, and column oven in the reported methods leads to the intricate and costlier analyte estimation which are [12,22].…”