Dionisio_2013_Biochimie_95_2376

GABAA receptors (GABAAR) mediate inhibitory neurotransmission in the human brain. Neurons modify subunit expression, cellular distribution and function of GABAAR in response to different stimuli, a process named plasticity. Human lymphocytes have a functional neuronal-like GABAergic system with GABAAR acting as inhibitors of proliferation. We here explore if receptor plasticity occurs in lymphocytes. To this end, we analyzed human T lymphocyte Jurkat cells exposed to different physiological stimuli shown to mediate plasticity in neurons: GABA, progesterone and insulin. The exposure to 100 muM GABA differently affected the expression of GABAAR subunits measured at both the mRNA and protein level, showing an increase of alpha1, beta3, and gamma2 subunits but no changes in delta subunit. Exposure of Jurkat cells to different stimuli produced different changes in subunit expression: 0.1 muM progesterone decreased delta and 0.5 muM insulin increased beta3 subunits. To identify the mechanisms underlying plasticity, we evaluated the Akt pathway, which is involved in the phosphorylation of beta subunits and receptor translocation to the membrane. A significant increase of phosphorylated Akt and on the expression of beta3 subunit in membrane occurred in cells exposed 15 h to GABA. To determine if plastic changes are translated into functional changes, we performed whole cell recordings. After 15 h GABA-exposure, a significantly higher percentage of cells responded to GABA application when compared to 0 and 40 h exposure, thus indicating that the detected plastic changes may have a role in GABA-modulated lymphocyte function. Our results reveal that lymphocyte GABAAR are modified by different stimuli similarly and by similar mechanisms to those in neurons. This property is of significance for the development of future therapies involving pharmacological modulation of the immune response.