| Literature DB >> 31959964 |
Riley E Perszyk1, Sharon A Swanger1,2,3,4, Chris Shelley1,5, Alpa Khatri1, Gabriela Fernandez-Cuervo6,7, Matthew P Epplin6, Jing Zhang1, Phuong Le1, Pernille Bülow8,9, Ethel Garnier-Amblard6, Pavan Kumar Reddy Gangireddy6, Gary J Bassell9, Hongjie Yuan1, David S Menaldino6, Dennis C Liotta6, Lanny S Liebeskind6, Stephen F Traynelis10.
Abstract
Allosteric modulators of ion channels typically alter the transitions rates between conformational states without changing the properties of the open pore. Here we describe a new class of positive allosteric modulators of N-methyl D-aspartate receptors (NMDARs) that mediate a calcium-permeable component of glutamatergic synaptic transmission and play essential roles in learning, memory and cognition, as well as neurological disease. EU1622-14 increases agonist potency and channel-open probability, slows receptor deactivation and decreases both single-channel conductance and calcium permeability. The unique functional selectivity of this chemical probe reveals a mechanism for enhancing NMDAR function while limiting excess calcium influx, and shows that allosteric modulators can act as biased modulators of ion-channel permeation.Entities:
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Year: 2020 PMID： 31959964 PMCID： PMC6986806 DOI： 10.1038/s41589-019-0449-5
Source DB: PubMed Journal: Nat Chem Biol ISSN： 1552-4450 Impact factor: 15.040