Glutamate receptor ion channels (GluRs) mediate excitatory neurotransmission at fast chemical synapses in the brain. Glutamate receptor subtypes are named for their selective agonists: NMDA, AMPA and Kainate. Although GluRs share a common architecture, the different subtypes have distinct kinetic properties. For example, the recovery of AMPA receptors from desensitization is two orders of magnitude faster than that of kainate receptors. Despite careful study (e.g. Weston et al., 2006), the molecular determinants of these differences remain unclear. We generated two chimeras with reciprocal exchanges between the ligand binding domains of an AMPA receptor subunit, GluA2 (Q, flip), and that of a kainate receptor subunit, GluK2. The chimera containing the binding domain of the GluA2 receptor in a GluK2 background was named B2P6 (Binding 2, Pore 6); the reverse chimera was named B6P2. We expressed the chimeras in HEK-293 cells and studied their properties in outside-out patches using a fast perfusion system at 23°C. Both chimeras exhibited rapid activation and desensitization like that of wild-type channels. The B2P6 chimera had kdes = 74 ± 3 s-1 (n = 7 patches), slightly slower than wild-type GluA2 (kdes =148 ± 12 s-1; Plested and Mayer, 2009). The reverse chimera, B6P2, desensitized faster, with kdes = 350 ± 10 s-1 (n = 5), similar to the reported data for GluK2 (170 ± 20 s-1; Plested and Mayer, 2007) Strikingly, rates of recovery from desensitization were fully exchanged between the two chimeras, being entirely determined by the identity of the ligand binding core. The B2P6 chimera recovered rapidly, krec = 64 ± 6 s-1 (n = 4 patches), even faster than wild-type GluA2 (28 ± 3 s-1; Plested and Mayer, 2009), and nearly 200-fold faster than for GluK2 (krec = 0.38 ± 0.07 s-1 Plested and Mayer, 2007). The B6P2 chimera recovered very slowly, with krec = 0.7 ± 0.1 s-1. This rate was very similar to the recovery of wild-type GluK2, and 40-fold slower than that of wild-type GluA2. The apparent affinity for glutamate at the B2P6 chimera was 350 ± 70 µM (n = 3), the same as for GluA2 wild-type channels when desensitization is blocked (300 µM; Zhang et al., 2006). The glutamate EC50 for the B6P2 chimera was 680 ± 140 µM (n = 3), similar to reported values for GluK2 (500 µM; Traynelis and Wahl, 1997). Activation by selective agonists and ion sensitivity were also exchanged between the chimeras, suggesting that the neurotransmitter binding sites and the active dimer arrangement were preserved in chimeras. These results show that the kinetic differences between AMPA and kainate receptors arise mainly from the ligand binding cores.