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 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 (). 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 (ICAN) and report for the first time the presence of a synaptic ICAN in the mammalian CNS. First, we have shown pharmacologically that activation of ICAN 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 ICAN 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 GABAA receptor antagonists. This current shows similar properties to the exogenously evoked ICAN: its reversal potential is close to the reversal potential of the 1S, 3R-ACPD-evoked ICAN, and it is G-protein- and Ca2+-dependent. Because the amplitude and duration of ICAN 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 synaptic ICAN, 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.
Congar
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Université René Descartes and Institut National de la Santé et de la Recherche Médicale Unité 29, 75674 Paris Cedex 14, France.
Leinekugel
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Ben-Ari
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Crépel
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D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002412:Cations / Q000378:metabolism*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
D002412:Cations; D018696:Neuroprotective Agents; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D002118:Calcium