The effect of internal GTPγs on GABA-release in cultured hippocampal neurons

The effects of presynaptic guanosine-5'-O-(3-thio)triphosphate (GTP gamma S) on GABAergic inhibitory postsynaptic currents (IPSCs) were studied in cultured hippocampal neurons using whole-cell recordings. Inclusion of GTP gamma S (0.5-1 mM) in the presynaptic electrode reduced both the amplitud...

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Bibliographic Details
Published in:Experimental brain research 2000-09, Vol.134 (2), p.204-211
Main Authors: JENSEN, K, LAMBERT, J. D. C, JENSEN, M. S
Format: Article
Language:English
Subjects:
Biological and medical sciences
Central nervous system
Central neurotransmission. Neuromudulation. Pathways and receptors
Fundamental and applied biological sciences. Psychology
GTP
Vertebrates: nervous system and sense organs
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Summary:The effects of presynaptic guanosine-5'-O-(3-thio)triphosphate (GTP gamma S) on GABAergic inhibitory postsynaptic currents (IPSCs) were studied in cultured hippocampal neurons using whole-cell recordings. Inclusion of GTP gamma S (0.5-1 mM) in the presynaptic electrode reduced both the amplitude and paired-pulse depression of IPSCs, indicating that the probability of GABA-release had been reduced. Presynaptic GTP gamma S increased the depression of IPSCs by the GABAB-receptor-agonist baclofen (10 mu M), and the effect of baclofen was poorly reversible after washing. Stimulation of the GABAergic neuron at 80 Hz for 1 s was accompanied by tetanic depression of the IPSCs by 52+6% and was followed by post-tetanic potentiation (PTP), reaching a peak value of 71+21% and lasting about 100 s. IPSCs evoked after tetanic stimulation were depressed and PTP was absent when tetanic stimulation was applied within 3 min after starting injection of GTP gamma S into the presynaptic neuron. At longer times, basal release underlying a single IPSC was depressed. This affected the ratios recorded in response to tetanic stimulations such that tetanic depression was abolished, while PTP increased to 117+34%. In conclusion, GTP gamma S reduces the probability of GABA-release in both a use- and time-dependent manner, most likely through an inhibitory action on presynaptic Ca super(2+)-influx through voltage-gated Ca super(2+) channels or an interaction with small GTP-binding proteins in the nerve terminals.
ISSN:0014-4819
1432-1106
DOI:10.1007/s002210000447