Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes

γ-aminobutyric acid (GABA) is the most prominent neuroinhibitory transmitter in the brain, where it activates neuronalGABA-A receptors (GABA-A channels) located at synapses and outside of synapses. The GABA-A receptors are primarytargets of many clinically useful drugs. In recent years, GABA has been shown to act as an immunomodulatory molecule. Wehave examined in human, mouse and rat CD4+ and CD8+ T cells which subunit isoforms of the GABA-A channels areexpressed. The channel physiology and drug specificity is dictated by the GABA-A receptor subtype, which in turn isdetermined by the subunit isoforms that make the channel. There were 5, 8 and 13 different GABA-A subunit isoformsidentified in human, mouse and rat CD4+ and CD8+ T cells, respectively. Importantly, the γ2 subunit that imposesbenzodiazepine sensitivity on the GABA-A receptors, was only detected in the mouse T cells. Immunoblots andimmunocytochemistry showed abundant GABA-A channel proteins in the T cells from all three species. GABA-activatedwhole-cell transient and tonic currents were recorded. The currents were inhibited by picrotoxin, SR95531 and bicuculline,antagonists of GABA-A channels. Clearly, in both humans and rodents T cells, functional GABA-A channels are expressed butthe subtypes vary. It is important to bear in mind the interspecies difference when selecting the appropriate animal modelsto study the physiological role and pharmacological properties of GABA-A channels in CD4+ and CD8+ T cells and whenselecting drugs aimed at modulating the human T cells function