1S,3R-ACPD-preferring inward current in rat dorsolateral septal neurons is mediated by a novel excitatory amino acid receptor.
Metabotropic glutamate receptors (mGluRs) form a receptor family that consists of diverse receptor subtypes; now, numbering 8--exclusive of splice variants. (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) has been suggested to be a selective agonist for the mGluRs. We have recently reported that, in rat dorsolateral septal nucleus (DLSN) neurones, a 1S,3R-ACPD-preferring inward current (ACPDi) persists in pertussis toxin-treated rats. We now report that this ACPDi-current: (1) persists in DLSN neurones dialyzed with a stable analog of GTP, namely, GTP gamma S; (2) exhibits a negative slope region with inward rectification in its I-V relationship; (3) persists in neurones superfused with tetrodotoxin or low calcium solutions; (4) is dependent upon both sodium and calcium ions; and (5) is independent of a reduction in temperature. Furthermore, pharmacological data suggest that this current may be activated by a unique type of excitatory amino acid (EAA) receptor, i.e. a receptor which prefers "metabotropic" EAA agonists and is insensitive to AP5 or CNQX. Activation by ACPD of inward currents associated with a conductance increase have also been reported at cultured mouse cerebellar Purkinje neurones; in slices of rat hippocampal CA1 neurones and slice cultures of hippocampal CA3 neurones. We suggest that this ACPDi current may play an important role within the CNS in the induction of long-term potentiation and other neurological processes; processes attributed previously to currents associated with NMDA receptor activation.
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031, USA.
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Gallagher
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D013696:Temperature; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D010566:Virulence Factors, Bordetella; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins