Pharmacological evidence that D-aspartate activates a current distinct from ionotropic glutamate receptor currents in Aplysia californica

Stephen L. Carlson, Andrew T. Kempsell, Lynne A. Fieber

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

D-Aspartate (D-Asp) activates a nonspecific cation current of unknown identity independent of L-glutamate (L-Glu) in neurons of Aplysia californica. Whole-cell voltage clamp studies were conducted using primary cultures of Aplysia buccal S cluster (BSC) neurons to characterize these receptor channels pharmacologically. The N-methyl-D-aspartate receptor (NMDAR) coagonist glycine potentiated D-Asp currents only at -30mV, while D-serine did not potentiate D-Asp currents at any amplitude. Portions of D-Asp currents were blocked by the L-Glu antagonists kynurenate, DL-2-amino-5-phosphonopentanoic acid (APV), (2S,3R)-1-(phenanthren-2-carbonyl)piperazine-2,3-dicarboxylic acid (PPDA), and 1,3-dihydro-5-[3-[4-(phenylmethyl)-1-2H-benzimidazol-2-one (TCS46b), suggesting that L-Glu channels, particularly NMDAR-like channels, may partially contribute to D-Asp whole-cell currents. In contrast, L-Glu currents were unaffected by APV, and showed greater block by kynurenate, suggesting that D-Asp and L-Glu act, in part, at different sites. The excitatory amino acid transport blocker DL-threo-b-Benzyloxyaspartic acid (TBOA) blocked a fraction of D-Asp currents, suggesting that currents associated with these transporters also contribute. Non-NMDA L-GluR antagonists that preferentially block alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptors significantly increased D-Asp currents, suggesting a possible allosteric potentiating effect of these antagonists on D-Asp receptors. L-Glu-induced currents were significantly reduced in the presence of bath-applied D-Asp, whereas bath-applied L-Glu had no effect on D-Asp-induced currents. The mixed effects of these agents on D-Asp-induced currents in Aplysia illustrate that the underlying channels are not uniformly characteristic of any known agonist associated channel type. D-Aspartate (D-Asp) activates a Na+ and K+ current of unknown identity independent of L-glutamate (L-Glu) in neurons of Aplysia californica. Portions of D-Asp currents were blocked by L-Glu antagonists including kynurenate and APV, but L-Glu currents were unaffected by APV, and showed greater block by kynurenate, suggesting that D-Asp and L-Glu may act at different sites. The mixed pharmacological results as well as an asymmetrical desensitization by D-Asp of L-Glu currents suggest that D-Asp channels in Aplysia are not uniformly characteristic of any known agonist-associated channel type.

Original languageEnglish (US)
Pages (from-to)391-401
Number of pages11
JournalBrain and Behavior
Volume2
Issue number4
DOIs
StatePublished - Jul 2012

Keywords

  • APV
  • Buccal ganglion
  • Coagonist
  • Electrophysiology
  • Mollusk
  • NMDA

ASJC Scopus subject areas

  • Behavioral Neuroscience

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