Abstract

The Xenopus oocyte expression system has been used to test for the existence in rat and Xenopus central nervous systems (CNS) of excitatory amino acid receptors (EAAR) that show sensitivity to both N-methyl-D-aspartate (NMDA) and L-kainate. Two to 15 days after injection of oocytes with rat brain poly(A+) RNA (or total RNA) and Xenopus CNS poly(A+) RNA, voltage-clamped oocytes were tested for EAAR expression by exposure to various excitatory amino acids (EAA). Responses to coapplication of NMDA and/or kainate were less than the sum of those obtained during application of each of these two EAA alone. In both cases, the antagonism was noncompetitive, although at millimolar concentrations, competitive antagonism was also observed. The extent of noncompetitive antagonism by NMDA of the response to kainate was proportional to an oocyte's sensitivity to NMDA. Oocytes injected with mRNA transcribed from the GluR1 clone encoding a rat non-NMDA receptor subunit did not respond to NMDA, and antagonism of the response to kainate occurred only with millimolar concentrations of NMDA and was competitive. Various explanations for these results are discussed. One possibility is that Xenopus oocytes injected with these vertebrate CNS RNA express a subpopulation of receptors containing kainate-sensitive and NMDA-sensitive subunits in addition to NMDA receptors and non-NMDA receptors. This explanation is supported by the observation that the NMDA antagonists MK-801 and magnesium antagonize part of the current induced by kainate, but only when NMDA is present.