Premium
Calcium/calmodulin‐dependent kinase II phosphorylation of the GABA A receptor α1 subunit modulates benzodiazepine binding
Author(s) -
Churn Severn B.,
Rana Aniruddha,
Lee Kangmin,
Parsons J. Travis,
De Blas Angel,
Delorenzo Robert J.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01032.x
Subject(s) - gabaa rho receptor , gabaa receptor , allosteric regulation , phosphorylation , microbiology and biotechnology , chemistry , calmodulin , allosteric modulator , biology , biochemistry , receptor , enzyme
γ‐Aminobutyric acid (GABA) is the primary neurotransmitter that is responsible for the fast inhibitory synaptic transmission in the central nervous system. A major post‐translational mechanism that can rapidly regulate GABA A R function is receptor phosphorylation. This study was designed to test the effect of endogenous calcium and calmodulin‐dependent kinase II (CaM kinase II) activation on both allosteric modulator binding and GABA A receptor subunit phosphorylation. Endogenous CaM kinase II activity was stimulated, and GABA A receptors were subsequently analyzed for bothallosteric modulator binding properties and immunoprecipitated and analyzed for subunit phosphorylation levels. A significant increase in allosteric‐modulator binding of the GABA A R was observed under conditions maximal for CaM kinase II activation. In addition, CaM kinase II activation resulted in a direct increase in phosphorylation of the GABA A receptor α1 subunit. The data suggest that the CaM kinase II‐dependent phosphorylation of the GABA A receptor α1 subunit modulated allosteric modulator binding to the GABA A receptor.