Activity-dependent regulation of GABAA receptor function mediated by a phosphorylation mechanism

MARÍA LAURA GUTIÉRREZ; MARÍA CELESTE FERRERI; MARÍA CLARA GRAVIELLE

Huerta Grande, Córdoba, Argentina

Congreso; Segunda reunion conjunta de la Sociedad Argentina de Neurociencias y el Taller Argentino de Neurociencias; 2010

Sociedad Argentina de Neurociencias y Taller Argentino de Neurociencias

Continuous activation of GABAA receptors under pathological and physiological conditions produces changes in receptor structure and/or function. Chronic exposure of neocortical cultures to GABA (48 h) induces down regulation of GABAA receptor number and uncoupling of GABA and benzodiazepine binding sites. A brief exposure to GABA (t1/2 3 min), however, induces uncoupling hours later without alterations in receptor number. This paradigm allowed us to study the uncoupling mechanism independently from the down regulation mechanism. In a previous study we found a decrease in mRNA and protein levels of certain GABAA receptor subunits and a reduction in the levels of á3-containing receptors. On the other hand, we demonstrated that PKA and PKC inhibitors block uncoupling induced by a brief GABA exposure. Since GABAA receptor function and intracellular trafficking are regulated by phosphorylation, the aim of this work was to study possible changes on the receptor phosphorylation state. We observed an increase in the phosphorylation degree of ã2 without changes in the phosphorylation state of â2 subunits. These results suggest that activation of PKA and PKC pathways are part of the uncoupling mechanism induced by GABAA receptor stimulation, probably by phosphorylation of some receptor subunits.