Activation of metabotropic glutamate receptors increase the frequency of spontaneous GABAergic currents through protein kinase A in neonatal rat hippocampal neurons.
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 gamma-aminobutyric acid (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 microM), 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 microM over control) was 2.6 +/- 1 (mean +/- SD), 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 microM) 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 microM), but not its analogue 1,9 dideoxyforskolin (30 microM), mimicked the effect of t-ACPD. Similar effects were obtained with 3-isobutyl-1-methylxanthine (IBMX, 200 microM). 6. The potentiating effect of t-ACPD on spontaneous GABAergic currents was prevented by Rp-cAMPS (30 microM), 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.
D000818:Animals; D000831:Animals, Newborn; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology*; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D017868:Cyclic AMP-Dependent Protein Kinases