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

PLoS One. 2012;7(8):e42959. doi: 10.1371/journal.pone.0042959. Epub 2012 Aug 21.

Abstract

γ-Aminobutyric acid (GABA) is the most prominent neuroinhibitory transmitter in the brain, where it activates neuronal GABA-A receptors (GABA-A channels) located at synapses and outside of synapses. The GABA-A receptors are primary targets of many clinically useful drugs. In recent years, GABA has been shown to act as an immunomodulatory molecule. We have examined in human, mouse and rat CD4(+) and CD8(+) T cells which subunit isoforms of the GABA-A channels are expressed. The channel physiology and drug specificity is dictated by the GABA-A receptor subtype, which in turn is determined by the subunit isoforms that make the channel. There were 5, 8 and 13 different GABA-A subunit isoforms identified in human, mouse and rat CD4(+) and CD8(+) T cells, respectively. Importantly, the γ2 subunit that imposes benzodiazepine sensitivity on the GABA-A receptors, was only detected in the mouse T cells. Immunoblots and immunocytochemistry showed abundant GABA-A channel proteins in the T cells from all three species. GABA-activated whole-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 but the subtypes vary. It is important to bear in mind the interspecies difference when selecting the appropriate animal models to study the physiological role and pharmacological properties of GABA-A channels in CD4(+) and CD8(+) T cells and when selecting drugs aimed at modulating the human T cells function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Female
  • Gene Expression Regulation*
  • Humans
  • Jurkat Cells
  • Male
  • Mice
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Transport
  • Rats
  • Receptors, GABA-A / genetics*
  • Receptors, GABA-A / metabolism
  • Species Specificity

Substances

  • Protein Isoforms
  • Receptors, GABA-A

Grant support

Human pancreatic lymph nodes were obtained from The Nordic network for Clinical Islet Transplantation, supported by the Swedish national strategic research initiative EXODIAB (Excellence of Diabetes Research in Sweden) and the Juvenile Diabetes Research Foundation. The authors thank the Swedish Research Council, Swedish Diabetes Research Foundation, The Ernfors Foundation, Uppsala University and EXODIAB for financial support. ZJ held a postdoctoral fellowship sponsored by EXODIAB and The Swedish Association for Medical Research (SSMF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.