Abstract
Glutamate delta‐1 receptor (delta1) is a member of the ionotropic glutamate receptor family and is expressed in the adult hippocampus and in the inner ear and has been shown to be important in high frequency hearing. Similar to its closest homologue, the delta2 receptor, no agonist induced currents are observed from delta1. The lurcher mutation present in the activation gate in the third transmembrane domain in the SYTANLAAF region in delta2 receptor converts it into a constitutively open cation permeating channel. To understand the structure and function of delta1 receptors we probed the conserved transmembrane domain 3 of the receptor mutating amino‐acids in the activation gate using site‐directed mutagenesis. Employing the two electrode voltage‐clamp technique, four mutants A650C, L652A, A654C and F655A were found to be constitutively open. Leak currents were partially blocked by pentamidine, NASP inhibited 10% of the currents. Studies of the crystal structure of the delta2 receptor agonist binding domain revealed that D‐serine binds to the ABD and inhibited spontaneous currents through delta2Lc. D‐serine inhibited currents through the chimeric delta1‐delta2Lc receptor suggesting residues forming the ABD in delta2 may be conserved in delta1 receptor. Additionally extracellular Ca 2+ may have similar potentiation effect as in Delta2 lurcher. Research support NARSAD.