1.A.10.1.23
Ionotropic glutamate receptor, GluR1 (GluR-1, GluR1-flip; GRIA1; GluH1; CTZ; GluA1) of 906 aas and 4 - 6 TMSs. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter, L-glutamate, induces a conformational change, leading to the opening of the cation-specific channel, thereby converting the chemical signal to an electrical impulse upon entry of Na⁺ and Ca²⁺. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, it shows resensitization characterized by a delayed accumulation of current flux upon continued application of glutamate (Kato et al. 2010). The polyamines, spermine, spermidine and putrescine can be drawn into the permeation pathway and get stuck, blocking the movement of other ions. The degree of this polyamine-mediated channel block is highly regulated by processes that control the free cytoplasmic polyamine concentration, the membrane potential, and the iGluR subunit composition (Bowie 2018). (-)-Arctigenin and a series of new analogues have been synthesised and tested for their potential as AMPA and kainate receptor antagonists of human homomeric GluA1 and GluK2 receptors, and thus potential drugs for epilepsy treatment (Rečnik et al. 2021). It may play a role in osteoporosis (Wu et al. 2023).