title: L-AP4 inhibits high voltage-activated Ca2+ currents in pyramidal cortical neurones.
abstract: We tested the ability of L-AP4 to modulate high voltage-activated (HVA) calcium (Ca2+) currents in pyramidal neurones acutely isolated from the adult rat (4-8 weeks). Whole cell recordings, with barium (Ba2+) ions as the charge carrier, were performed. L-AP4 reduced HVA Ca2+ conductances in 86% of the recorded cells. Saturating concentrations of L-AP4 inhibited about 21% of the current (+/- 8.3%, n = 8), although great variability was observed. Interestingly, low micromolar concentrations of (1S,3R)-1-aminocyclo-pentane-1,3-dicarboxylic acid (1S,3R-ACPD) and (2S,3S,4R)-alpha-(carboxy-cyclopropyl)-glycine (1-CCGI) had weaker effects than L-AP4. MAP4 fully antagonized the L-AP4-mediated reduction of HVA Ca2+ currents. These findings suggest the involvement of the AP4-sensitive receptor in the control of both cellular excitability and transmitter release in rat neocortical neurones.
authors.affiliation: Clinica Neurologica, Dip. Sanità Pubblica, Università di Roma Tor Vergata, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Stefani
authors.forename: F
authors.initials: F
authors.lastname: Spadoni
authors.forename: G
authors.initials: G
authors.lastname: Bernardi
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D000613:Aminobutyrates / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists
chemical_list: D000600:Amino Acids, Dicarboxylic; D000613:Aminobutyrates; D002121:Calcium Channel Blockers; D018690:Excitatory Amino Acid Agonists; D008869:Microtubule-Associated Proteins; D009498:Neurotoxins; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C035261:(alpha-carboxycyclopropyl)glycine; D001464:Barium; C012729:2-amino-4-phosphonobutyric acid