Persistent current oscillations produced by activation of metabotropic glutamate receptors in immature rat CA3 hippocampal neurons

1. The single-electrode voltage-clamp technique was used to study the effects of the metabotropic glutamate receptors (mGluRs) agonist 1S,3R-1- aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD, 3-10 μM) on CA3 hippocampal neurons during the 1st 10 days of postnatal (P) life and in adulthood. 2. Repeated applications of 1S,3R-ACPD, in the presence of tetrodotoxin (TTX, 1 μM), tetraethylammonium chloride (TEACI 10 mM), and CsCl (2 mM), induced in immature but not in adult neurons periodic inward currents (PICs) that persisted for several hours after the last application of the agonist. 3. PICs, which were generated by nonspecific cationic currents, reversed polarity at 2.8 ± 3 (SD) mV. They were reversibly blocked by kynurenic acid (1 mM), suggesting that they were mediated by glutamate acting on ionotropic receptors. They were also abolished in a nominally Ca2+-free medium. 4. PICs were irreversibly abolished by thapsigargin (10 μM) but were unaffected by ryanodine (10-40 μM). Caffeine (2 mM) also reversibly blocked PICs; this effect was independent from adenosine 3',5'- cyclic monophosphate (cAMP) accumulation inhibition of voltage-dependent Ca2+current, or blockade of adenosine receptors. 5. We suggest that, in neonatal slices, mGluRs-induced PICs are triggered by elevation of [Ca2+](i), after mobilization of Ca2+from inositol 1,4,5-trisphosphate (InsP3)-sensitive stores. This will lead to a persistent, pulsatile release of glutamate from presynaptic nerve terminals, a phenomenon that is probably maintained via a calcium-induced-calcium release process.