Cloning and characterization of χ-1: A developmentally regulated member of a novel class of the ionotropic glutamate receptor family

Abstract

Ionotropic glutamate receptors are composed of homomeric or heteromeric configurations of glutamate receptor subunits. We have cloned a member of a novel class of the rat ionotropic glutamate receptor family, termed χ-1. This subunit exhibits an average identity of 27% to NMDA subunits and 23% to non-NMDA subunits. Regional transcript levels of χ-1 are elevated just prior to and during the first postnatal week, with the highest levels present in the spinal cord, brainstem, hypothalamus, thalamus, CA1 field of the hippocampus, and amygdala. The spatial distribution of χ-1 expression is similar from postnatal day 1 (P1) to adulthood. However, transcript levels decline sharply between P7 and P14 and remain attenuated into adulthood. Functional expression studies in Xenopus oocytes injected with in vitro transcribed χ-1 RNA did not demonstrate agonist-activated currents. Pairwise expression of χ-1 with members of the AMPA, KA, or δ class of glutamate receptor subunits either failed to generate agonist-activated currents or failed to alter the underlying current generated by the coexpressed subunit. However, coexpression of χ-1 with subunits forming otherwise functional NMDA receptors resulted in an inhibition of current responses. Since χ-1 did not alter the currents generated by non-NMDA subunits, this suggests that χ-1 may specifically interact with NMDA receptor subunits. Further characterization will be required to establish the precise role of this glutamate receptor subunit in neuronal signaling.