Ionotropic glutamate receptors critically shape synaptic signals in the CNS. Contrary to the well-characterized AMPA, kainate, and NMDA receptor subtypes, no agonist-induced ionotropic function of the two delta receptor subunits, delta1 and delta2, has
been described. To investigate the capability of single delta receptor domains to support ionotropic function, the ion pore, the ligand binding domain (LBD), and the linkers that connect the two, were examined by domain transplantation.
The most profound in_uence on channel function was observed upon transplantation of the three linkers. All decisively a_ected receptor functionality, agonist potency, and desensitization.
The delta2 subunit formed functional glutamate-gated ion channels when its LBD was exchanged for that of GluR6. This chimera allowed to characterize agonist-controlled current through a delta2 ion channel, suggesting that the key to delta receptor
function is to be found within their LBD.