Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336912
Title: GABAA-mediated synaptic activity in rat hippocampal neurones in vitro and its modulation by other neurotransmitters and second messengers
Author: Sciancalepore, Marina
ISNI:       0000 0001 3557 1290
Awarding Body: Open University
Current Institution: Open University
Date of Award: 1997
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Abstract:
The patch-clamp technique (whole-cell and outside-out configurations) has been used to characterize spontaneous ɣ-aminobutyric acid A (GABAA) receptor mediated currents in pyramidal cells of thin hippocampal slices obtained from neonatal rats. In early postnatal life, GABA is the main excitatory neurotransmitter on hippocampal pyramidal cells. The frequency distribution histogram of spontaneous GABAergic currents could be fitted by a single exponential function revealing the random nature of these events. The present results demonstrate that in tetrodotoxin (TTX) solution spontaneous GABAA receptor mediated miniature postsynaptic currents (mPSCs) were present. At -70 mV the first peak in the current amplitude distribution was 16 ± 6 pA (n =13). This value was similar to that found for GABAergic currents (14 ± 6 pA) elicited by low intensity extracellular stimulation, suggesting that this effect was due to the release of elementary units of GABA. In outside-out patches, GABA activated single-channel events of 24 and 35 pS conductance. Assuming that a postsynaptic current of 15 pA corresponds to a single quantum of GABA, one could calculate that one quantal current represents the simultaneous opening of 6 to 9 GABAA receptor channels in the postsynaptic cell. The metabotropic Glutamate Receptor (mGluR) agonist, 1 -aminocyclopentane-1,3-dicarboxylic acid (t-ACPD), induced an increase in frequency but not in amplitude of spontaneously occurring GABAergic currents; this potentiating effect was blocked by the Protein Kinase A (PKA) antagonist Rp-adenosine 3', 5'-cyclic monophosphotioate triethylamine (Rp-cAMPS), suggesting that glutamate, acting on mGluRs, is able to increase GABA release through the metabolic pathway which involves PKA. The potentiating effect of t-ACPD was not observed in TTX solution indicating that the site of action of the mGluR agonist is probably located at the somatodendritic level and not on the nerve terminals ofGABAergic intemeurones. In the presence of forskolin, which increases intracellular cyclic AMP (cAMP) levels, a rise in frequency but not in amplitude of miniature GABAA receptor mediated currents was observed, an effect that was prevented by the selective PKA antagonist Rp-cAMPS. These experiments suggest that presynaptic mGluRs localized on GABAergic interneurones may facilitate the activity of these cells and their release of GABA through cAMP-dependent PKA. Moreover, PKA may interfere directly with the mechanism of GABA release as demonstrated by its action on miniature events. The present results provide new evidence that the release of a major neurotransmitter such as GABA is up-regulated by another neurotransmitter namely Glutamate, thus demonstrating an important reinforcement of excitatory signals during an early stage of brain development.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.336912  DOI:
Keywords: Biophysics
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