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M Farrant

Publications and source records attributed to M Farrant.

23 records · Page 2Linked to original sources
PubMed1989

Neuronal activity, amino acid concentration and amino acid release in the substantia nigra of the rat after sodium valproate.

The effects of sodium valproate on extracellularly recorded spontaneous neuronal activity and striatal-evoked inhibition in the substantia nigra zona reticulata of the rat were compared with its effects on the tissue concentration of endogenous amino acids and their spontaneous release into perfusates of this region obtained with a push-pull cannula. Valproate (200 mg/kg i.p.) produced a rapid and sustained reduction in the firing rate of all reticulata neurones tested and a concomitant increase in the duration of striatal-evoked inhibition. No change in the spontaneous release of any amino acid was observed. A significant elevation of nigral gamma-aminobutyric acid concentration was seen in both anaesthetized and non-anaesthetized animals, but this occurred only after 60 minutes. Valproate produced a rapid decline in nigral aspartate in non-anaesthetized but not in anaesthetized animals. The results of this study suggest that the acute depressant effect of valproate is unrelated to its ability to alter the concentration of GABA or aspartate in brain and is most likely due to a postsynaptic action.

Action Potentials↗
PubMed1989

Compartmental distribution of endogenous amino acids in the substantia nigra of the rat.

Using a push-pull cannula we have monitored the spontaneous efflux of 8 endogenous amino acids into perfusates of the substantia nigra of the rat. The extracellular concentrations of the amino acids were estimated and compared to their respective tissue levels. High intra-/extracellular concentration ratios were found for gamma-aminobutyric acid (GABA), aspartate, glutamate and taurine. Much lower values were found for glycine, alanine, serine and glutamine. These results provide evidence for possible neurotransmitter roles for aspartate, glutamate and taurine in the substantia nigra in addition to that, long recognized, for GABA.

Amino Acids↗
PubMed1988

"Run-down" of gamma-aminobutyric acidA receptor function during whole-cell recording: a possible role for phosphorylation.

When using whole-cell recording methods and a minimal intracellular medium containing only inorganic ions, ethyleneglycolbis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, we have observed a time-dependent decrease in the responsiveness of cultured chick spinal cord neurons to gamma-aminobutyric acid (GABA). The current evoked by 30 microM GABA progressively declined to approximately 30% of its initial value after five applications at 10-min intervals. This was accompanied by an equivalent decline in the GABA-evoked membrane conductance. "Run-down" of the response was reduced when Mg2+-ATP was present in the pipet solution. Inclusion of ATP-gamma-S, an analog that donates a thiophosphate group resistant to hydrolysis, also reduced run-down. The nonhydrolyzable analog beta, gamma-imidoadenosine-5'-triphosphate was without effect. These results suggest that an ATP-dependent process, possibly phosphorylation, is involved in the maintenance of GABAA receptor function.

Adenosine Triphosphate↗
PubMedDate not supplied

NMDA receptor diversity in the cerebellum: identification of subunits contributing to functional receptors.

Recent studies of N-methyl-D-aspartate (NMDA) receptors have led to the suggestion that there are two distinct classes of native NMDA receptors, identifiable from their single-channel conductance properties. 'High-conductance' openings arise from NR2A- or NR2B-containing receptors, and 'low-conductance' openings arise from NR2C- or NR2D-containing receptors. In addition, the low-conductance channels show reduced sensitivity to block by Mg2+. The readily identified cell types and simple architecture of the cerebellum make it an ideal model system in which to determine the contribution of specific subunits to functional NMDA receptors. Furthermore, mRNA for all of these four NR2 subunits are represented in this brain region. We have examined NMDA channels in Purkinje cells, deep cerebellar nuclei (DCN) neurons and Golgi cells. First we find that NR2D-containing NMDA receptors give rise to low-conductance openings in cell-attached recordings from Purkinje cells. The characteristic conductance of these events cannot, therefore, be ascribed to patch excision. Second, patches from some DCN neurons exhibit mixed populations of high- and low-conductance openings. Third, Golgi cells also exhibit a mixed population of high- and low-conductance NMDA receptor openings. The features of these low-conductance openings are consistent with the presence of NR2D-containing NMDA receptors, as suggested by in situ hybridization data. On the other hand the existence of high-conductance channels, with properties typical of NR2B-containing receptors, was not expected. Our results provide new evidence about the subunit composition of NMDA receptors in identified cerebellar cells, and suggest that examination of single-channel properties is a potentially powerful approach for determining the possible subunit composition of native NMDA receptors.

Animals↗