AMPA receptor modulation by cornichon-2 dictated by transmembrane AMPA receptor regulatory protein isoform.
Eur J Neurosci
; 35(2): 182-94, 2012 Jan.
Article
in En
| MEDLINE
| ID: mdl-22211840
ABSTRACT
Transmembrane AMPA receptor regulatory proteins (TARPs) are auxiliary subunits that modulate AMPA receptor trafficking, gating and pharmacology throughout the brain. Why cornichon-2 (CNIH-2), another AMPA receptor-associated protein, modulates AMPA receptor gating and pharmacology in hippocampal neurons but not cerebellar granule neurons remains unresolved. Here, we report that CNIH-2 differentially impacts Type-Ia (γ-2 or γ-3) vs. Type-Ib (γ-4 or γ-8) TARP-containing AMPA receptors. Specifically, with AMPA receptors comprising γ-2, the cerebellar-enriched TARP isoform, CNIH-2 decreases I(KA) /I(Glu) ratio and decreases cyclothiazide efficacy while having minimal impact on recovery from desensitization and deactivation kinetics. By contrast, with AMPA receptors comprising γ-8, the hippocampal-enriched TARP isoform, we find that CNIH-2 slows deactivation kinetics, increases cyclothiazide potency and occludes a novel AMPA receptor kinetic phenomenon, namely resensitization. Additionally, we find that CNIH-2 differentially modulates the glutamate off-kinetics of γ-8-containing, but not γ-2-containing, AMPA receptors in a manner dependent upon the duration of agonist application. Together, these data demonstrate that the modulation of AMPA receptors by CNIH-2 depends upon the TARP isoform composition within the receptor complex.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
/
Egg Proteins
/
Receptors, AMPA
/
Membrane Proteins
/
Neurons
Limits:
Humans
Language:
En
Journal:
Eur J Neurosci
Journal subject:
NEUROLOGIA
Year:
2012
Document type:
Article
Affiliation country:
United States