The effect of internal GTPgammaS on GABA-release in cultured hippocampal neurons.
The effects of presynaptic guanosine-5'-O-(3-thio)triphosphate (GTPgammaS) on GABAergic inhibitory postsynaptic currents (IPSCs) were studied in cultured hippocampal neurons using whole-cell recordings. Inclusion of GTPgammaS (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 GTPgammaS increased the depression of IPSCs by the GABA(B)-receptor-agonist baclofen (10 microM), 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 GTPgammaS 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, GTPgammaS reduces the probability of GABA-release in both a use- and time-dependent manner, most likely through an inhibitory action on presynaptic Ca2+-influx through voltage-gated Ca2+ channels or an interaction with small GTP-binding proteins in the nerve terminals.
Jensen
K
K
Department of Physiology, University of Aarhus, Denmark.
Lambert
J D
JD
Jensen
M S
MS
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002478:Cells, Cultured / Q000378:metabolism; D004347:Drug Interactions / Q000502:physiology; D004558:Electric Stimulation; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D016244:Guanosine 5'-O-(3-Thiotriphosphate); D005680:gamma-Aminobutyric Acid; D001418:Baclofen