Interleukin-2 inhibits NMDA receptor-mediated currents directly and may differentially affect subtypes.
Using whole-cell patch-clamp recordings, this study investigated the effects of interleukin-2 (IL-2) on N-methyl-d-aspartate (NMDA) receptor-mediated currents (I(NMDA)) in rat cultured hippocampal neurons and human embryonic kidney (HEK) 293 cells expressing recombinant NMDA receptors. We found that IL-2 (0.01-1ng/ml) immediately and significantly decreased peak I(NMDA) in cultured neurons. Interestingly, the peak I(NMDA) induced in HEK 293 cells was also inhibited by IL-2. We also found that IL-2 differentially decreased the peak amplitudes of NR2A- and NR2B-containing NMDA receptor-mediated currents (I(NR2A) and I(NR2B)) by 54+/-5% and 30+/-4%, respectively. These results provide new evidence that IL-2 induces rapid inhibition of peak currents of NMDA receptor-mediated responses with possible NR1/NR2A and NR1/NR2B subtype-differentiation, and suggest that the inhibition is mediated by direct interaction between IL-2 and NMDA receptors.
Shen
Yi
Y
Department of Neurobiology, Institute for Neuroscience, Zhejiang University School of Medicine, Hangzhou 310058, China.
Zhu
Li-Jun
LJ
Liu
Shuang-Shuang
SS
Zhou
Su-Ya
SY
Luo
Jian-Hong
JH
D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D015640:Ion Channel Gating; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology*
D007376:Interleukin-2; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D020033:Protein Isoforms; D016194:Receptors, N-Methyl-D-Aspartate