CLONING AND CHARACTERIZATION OF CHI-1 - A DEVELOPMENTALLY-REGULATED MEMBER OF A NOVEL CLASS OF THE IONOTROPIC GLUTAMATE-RECEPTOR FAMILY

Ionotropic glutamate receptors are composed of homomeric or heteromeri c configurations of glutamate receptor subunits. We have cloned a memb er of a novel class of the rat ionotropic glutamate receptor family, t ermed chi-1. This subunit exhibits an average identity of 27% to NMDA subunits and 23% to non-NMDA subunits. Regional transcript levels of c hi-1 are elevated just prior to and during the first postnatal week, w ith the highest levels present in the spinal cord, brainstem, hypothal amus, thalamus, CA1 field of the hippocampus, and amygdala. The spatia l distribution of chi-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 st udies in Xenopos oocytes injected with in vitro transcribed chi-1 RNA did not demonstrate agonist-activated currents. Pairwise expression of chi-1 with members of the AMPA, KA, or delta class of glutamate recep tor subunits either failed to generate agonist-activated currents or f ailed to alter the underlying current generated by the coexpressed sub unit. However, coexpression of chi-1 with subunits forming otherwise f unctional NMDA receptors resulted in an inhibition of current response s. Since chi-1 did not alter the currents generated by non-NMDA subuni ts, this suggests that chi-1 may specifically interact with NMDA recep tor subunits. Further characterization will be required to establish t he precise role of this glutamate receptor subunit in neuronal signali ng.