Modulation of AMPA and NMDA responses in rat spinal dorsal horn neurons by trans-1-aminocyclopentane-1,3-dicarboxylic acid

Abstract

In freshly isolated spinal dorsal horn (DH) neurons (laminae I–IV) of the young rat the effects of 25–100 μM of (±)- trans-1-aminocyclopentane-1,3-dicarboxylic acid ( trans-ACPD), 1 S,3 R-ACPD and 1 R,3 S-ACPD, a metabotropic glutamate receptor (mGluR) agonist, on inward currents induced by glutamate (Glu), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N- methyl- d-aspartate (NMDA) and kainate were studied under whole-cell voltage-clamp conditions. When the cells were clamped to −60 mV, the racemic mixture and both stereo isomers of trans-ACPD increase the responses elicited by Glu, AMPA, and NMDA, but little those of kainate. In addition, quisqualate (10–50 μM), in the presence of CNQX (5–20 μM) or NBQX (5 μM), potentiated NMDA-induced currents. The enhancing effect lasted 10–75 min, depending upon both dose and length of application. In a smaller proportion of dorsal horn neurons, the enhancing effect was preceded by a transient depression of the responses to Glu, AMPA, and NMDA. 2-Amino-3-phosphonopropionic acid (L-AP 3), a putative antagonist of mGluR exerted little effect on responses to AMPA itself, but reduced or prevented the enhancing effect of 1 S,3 R-ACPD. It is concluded that activation of a metabotropic glutamate receptor by trans-ACPD, and its two enantiomers, may mediate the enhancement of AMPA and NMDA responses in acutely isolated rat spinal dorsal horn neurons. These results are consistent with the possibility that the activation of metabotropic glutamate receptor may contribute to the regulation of the strength of excitatory amino-mediated primary afferent neurotransmission, including nociception.