Pharmacological evidence that D‐aspartate activates a current distinct from ionotropic glutamate receptor currents inAplysia californica

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Abstract
D‐Aspartate (D‐Asp) activates a nonspecific cation current of unknown identity independent of L‐glutamate (L‐Glu) in neurons ofAplysia californica. Whole‐cell voltage clamp studies were conducted using primary cultures ofAplysiabuccal 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 −30 mV, 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 inAplysiaillustrate that the underlying channels are not uniformly characteristic of any known agonist associated channel type.

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