A LONG-LASTING CALCIUM-ACTIVATED NONSELECTIVE CATIONIC CURRENT IS GENERATED BY SYNAPTIC STIMULATION OR EXOGENOUS ACTIVATION OF GROUP-I METABOTROPIC GLUTAMATE RECEPTORS IN CA1 PYRAMIDAL NEURONS

We have shown previously that a selective metabotropic glutamate recep tor (mGluR) agonist, 1S,3R-1-aminocyclopentane-1 ,3-dicarboxylate (1S, 3R-ACPD), evokes an inward current in CA1 pyramidal neurons of rat hip pocampal slices in the presence of K+ channel blockers (Crepel et al., 1994). This current has been characterized as a Ca2+-activated nonsel ective 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 t he first time the presence of a synaptic I-CAN in the mammalian CNS. F irst, we have shown pharmacologically that activation of I-CAN by 1S,3 R-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 isola ted a slow synaptic inward current evoked by a high-frequency stimulat ion 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-evoked I-CAN and it is G-protein- and Ca2+-dependent. Because the amplitude and duration of I-CAN increa sed in the presence of a glutamate uptake blocker, we suggest that thi s synaptic current is generated via the activation of mGluRs. We propo se that the synaptic I-CAN, activated by a brief tetanic stimulation a nd leading to a long-lasting inward current, may be involved in neuron al plasticity and synchronized network-driven oscillations.