Abstract

We have shown previously that a selective metabotropic glutamate receptor (mGluR) agonist, 1S,3R-1-aminocyclo-pentane-1,3-dicarboxylate (1S,3R-ACPD), evokes an inward current in CA1 pyramidal neurons of rat hippocampal slices in the presence of K⁺ channel blockers (Crépel et al., 1994). This current has been characterized as a Ca²⁺-activated nonselective cationic (CAN) current. Using whole-cell patch-clamp recordings and intracellular dialysis, we now have identified the mGluR subtype and the mechanisms underlying the CAN current (I_CAN) and report for the first time the presence of a synaptic I_CANin the mammalian CNS. First, we have shown pharmacologically that activation of I_CAN by 1S,3R-ACPD involves the group I mGluRs (and not the groups II and III) and a G-protein-dependent process. We also report that I_CAN is modulated by the divalent cations (Mg²⁺, Cd²⁺, and Zn²⁺). Second, we have isolated a slow synaptic inward current evoked by a high-frequency stimulation in the presence of K⁺ channel blockers, ionotropic glutamate, and GABA_A receptor antagonists. This current shows similar properties to the exogenously evoked I_CAN: its reversal potential is close to the reversal potential of the 1S,3R-ACPD-evokedI_CAN, and it is G-protein- and Ca²⁺-dependent. Because the amplitude and duration of I_CAN increased in the presence of a glutamate uptake blocker, we suggest that this synaptic current is generated via the activation of mGluRs. We propose that the synapticI_CAN, activated by a brief tetanic stimulation and leading to a long-lasting inward current, may be involved in neuronal plasticity and synchronized network-driven oscillations.