Activation of metabotropic glutamate receptors increase the frequency of
spontaneous GABAergic currents through protein kinase A in neonatal rat
hippocampal neurons.
Sciancalepore, M., F. Stratta, N.D. Fisher, and E. Cherubini.
Biophysics Laboratory, International School for Advanced Studies (SISSA),
Via Beirut 2/4, 34014 Trieste, Italy.
APStracts 2:0146N, 1995.
SUMMARY AND CONCLUSIONS
1. The tight-seal whole cell recording technique was used to study the effects
of the metabotropic glutamate receptor (mGluR) agonist, trans -1-
aminocyclopentane-1,3-dicarboxylic acid ( t -ACPD) on spontaneous GABA-
mediated synaptic currents in neonatal rat CA1 hippocampal neurons in slices
obtained from postnatal (P) days P6-P12. 2. Bath application of t -ACPD (3-30
[mu]M), in the presence of kynurenic acid, induced a concentration-dependent
increase in frequency but not in amplitude of spontaneous GABAergic currents.
The mean frequency ratio ( t -ACPD 10[mu]M over control) was 2.6 +/- 1,
whereas the mean amplitude ratio was 1.1 +/- 0.3. 3. The effect of t -ACPD was
partially antagonized by the mGluR antagonist (RS)-[alpha]-methyl-4-
carboxyphenylglycine (MCPG, 1 mM). 4. t -ACPD (10-30 [mu]M) did not modify the
frequency of miniature GABAergic synaptic currents recorded in tetrodotoxin
(the mean frequency ratio of t -ACPD over control was 0.7 ¯+ 0.3). 5.
Forskolin (30 [mu]M) but not its analogue 1,9 dideoxyforskolin (30[mu]M)
mimicked the effect of t -ACPD. Similar effects were obtained with 3-isobutyl-
1-methylxanthine (IBMX, 200 [mu]M). 6. The potentiating effect of t -ACPD on
spontaneous GABAergic currents was prevented by Rp-cAMPS (30[mu]M), a specific
antagonist of protein kinase A. This suggests that, mGluRs localized at the
soma-dendritic level of GABAergic interneurons and positively coupled to
cyclic AMP may modulate GABA release during a critical period of postnatal
development.
Received 16 December 1994; accepted in final form 25 April 1995.
APS Manuscript Number J785-4.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 16 May 1995.