title: T-cell receptor activation decreases excitability of cortical interneurons by inhibiting α7 nicotinic receptors.
abstract: Many proteins in the immune system are also expressed in the brain. One such class of immune proteins are T-cell receptors (TCRs), whose functions in T lymphocytes in adaptive immunity are well characterized. In the brain, TCRs are confined to neocortical neurons, but their functional role has not been determined. In mouse layer 1 neocortical neurons, TCR activation inhibited α7 nicotinic currents. TCRs modulated α7 currents via tyrosine phosphorylation of α7 nicotinic receptors (nAChRs) through src tyrosine kinases because eliminating lck kinase expression, coexpressing fyn kinase dead, or mutating tyrosine to alanine in α7 blocked the effect of TCR activation. We found that TCR stimulation decreased surface α7 nAChRs and reduced single-channel conductance. These results reveal that TCRs play a major role in the modulation of cholinergic neurotransmission in the brain mediated by α7 nAChRs and that this has a profound effect on regulating neuronal excitability.
authors.affiliation: Department of Biology and Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, V8W 3N5, Canada.
authors.forename: Pragya
authors.initials: P
authors.lastname: Komal
authors.forename: Geoff
authors.initials: G
authors.lastname: Gudavicius
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Nelson
authors.forename: Raad
authors.initials: R
authors.lastname: Nashmi
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007395:Interneurons / Q000378:metabolism*; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019579:Neocortex / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D011948:Receptors, Antigen, T-Cell; D064569:alpha7 Nicotinic Acetylcholine Receptor