Calcium/calmodulin‐dependent kinase II phosphorylation of the GABAA receptor α1 subunit modulates benzodiazepine binding

• Published in: Journal of neurochemistry Vol. 82; no. 5; pp. 1065 - 1076
• Main Authors: Churn, Severn B., Rana, Aniruddha, Lee, Kangmin, Parsons, J. Travis, De Blas, Angel, Delorenzo, Robert J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.2002; Blackwell
• Subjects: allosteric modulator; Aminoacid receptors (glycine, glutamate, gaba); Biological and medical sciences; Cell receptors; Cell structures and functions; Fundamental and applied biological sciences. Psychology; immunoprecipitation; Molecular and cellular biology; photoaffinity labeling; receptor binding; receptor solubilization; receptor subunits; receptor solubilization; Phosphorylation; calmodulin-dependent protein kinase; photo- affinity labeling; Rat; Enzyme; Transferases; Rodentia; Central nervous system; Benzodiazepine receptor; Subunit; Encephalon; allosteric modulator; Vertebrata; Mammalia; Synaptic transmission; immunoprecipitation; Neurotransmitter; GABA; receptor binding; receptor subunits; Gabaergic receptor A; Ca
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2002.01032.x

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 GABAAR 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 GABAA receptor subunit phosphorylation. Endogenous CaM kinase II activity was stimulated, and GABAA 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 GABAAR 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 GABAA receptor α1 subunit. The data suggest that the CaM kinase II‐dependent phosphorylation of the GABAA receptor α1 subunit modulated allosteric modulator binding to the GABAA receptor.