Cations But Not Anions Regulate the Responsiveness of Kainate Receptors

• DOI: 10.1523/jneurosci.4314-10.2011
• Publication Date: 2011-02-09T17:27:51Z
• Authors: David M. MacLean; Adrian Y. C. Wong; Anne-Marie Fay; Derek Bowie
• Keywords: Kainate receptor; Ionotropic glutamate receptor

Kainate-selective ionotropic glutamate receptors are unique among ligand-gated ion channels in their obligate requirement of external anions and cations for activation. Although it is established that the degree kainate receptor (KAR) activation shaped by chemical nature agonist molecule, possible complementary role ions has yet to be examined. Here we show but not regulate responsiveness a range full partial agonists acting on rat GluK2 receptors. This observation unexpected as previous work assumed affect KARs an identical manner through functionally coupled binding sites. However, our data demonstrate anion- cation-binding pockets behave discretely. We suggest uniquely pregating or flipping step impacts closed-cleft stability agonist-binding domain (ABD). model departs from proposal KAR efficacy governed closure elicited ABD ligand binding. Our findings are, however, line with recent studies Cys-loop suggesting "flipping" mechanism been conserved structurally diverse channel families common means regulating neurotransmitter behavior.