Stargazin differentially modulates ampakine gating kinetics and pharmacology.

Stargazin differentially modulates ampakine gating kinetics and pharmacology. Biochem Pharmacol. 2018 Jan 09;: Authors: Radin DP, Li YX, Rogers G, Purcell R, Lippa A Abstract It was previously reported that Stargazin (STG) enhances the surface expression of AMPA receptors, controls receptor gating and slows channel desensitization as an auxiliary subunit of the receptors. Ampakines are a class of AMPA receptor positive allosteric modulators that modify rates of transmitter binding, channel activity and desensitization parameters. As such, they have shown efficacy in animal models of neurodegenerative diseases, where excitatory synaptic transmission is compromised. Given the functional similarities between STG and ampakines, the current study sought to probe interactions between STG and ampakine gating properties. The effects of the high impact ampakines, CX614 and cyclothiazide (CTZ), were compared on homomeric GluR1-flip (Glur1i) and GluR2-flop (Glur2o) receptors expressed on HEK293 cells by transient transfection with or without STG gene. STG dramatically enhanced the surface expression of AMPA receptors and increased glutamate-induced steady-state currents during desensitization. STG also increased ratios of 500 μM kainate and 500 μM glutamate activated steady-state currents. STG reduced association rates of ampakines and differentially affected the dissociation rates for both CX614 and CTZ on desensitized receptors. The estimat...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research