PRIMARY STRUCTURE AND FUNCTIONAL EXPRESSION OF THE AMPA/KAINATE RECEPTOR SUBUNIT 2 FROM HUMAN BRAIN

A FULL-LENGTH cDNA clone encoding the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/ kainate (KA) receptor subunit 2 (HBGR2) was isolated from a human brain cDNA library. The HBGR2 cDNA has an open reading frame of approximate to 2.7 kb that codes for an 883-residue protein. At the amino acid level, HBGR2 is 98% identical to its rat counterpart GluR2, and 69% to the AMPA/KA receptor subunit 1 from human brain (HBGR1). Injection of cRNA transcripts from the HBGR2 into oocytes produces barely detectable kainate-activated ionic currents, indicating that the HBGR2 subunit alone weakly expresses homomeric receptor channels. Coexpression of HBGR2 and HBGR1 transcripts, however, evokes kainate-dependent currents which activate at higher agonist concentration than those required by homomeric HBGR1 receptor channels. Coexpressed receptors display a linear current-to-voltage relationship at variance with the inwardly rectifying profile exhibited by HBGR1 homomers. Hence, the HBGR2 subunit co-assembles with the HBGR1 subunit to form heteromeric receptor channels akin to the glutamate receptors from rodent brain.