Bröker-Lai Jenny, Kollewe Astrid, Schindeldecker Barbara, Pohle Jörg, Nguyen Chi Vivan, Mathar Ilka, Guzman Raul, Schwarz Yvonne, Lai Alan, Weißgerber Petra, Schwegler Herbert, Dietrich Alexander, Both Martin, Sprengel Rolf, Draguhn Andreas, Köhr Georg, Fakler Bernd, Flockerzi Veit, Bruns Dieter, Freichel Marc
Institute of Pharmacology, Heidelberg University, Heidelberg, Germany.
Institute of Physiology, University of Freiburg, Freiburg, Germany.
EMBO J. 2017 Sep 15;36(18):2770-2789. doi: 10.15252/embj.201696369. Epub 2017 Aug 8.
Canonical transient receptor potential (TRPC) channels influence various neuronal functions. Using quantitative high-resolution mass spectrometry, we demonstrate that TRPC1, TRPC4, and TRPC5 assemble into heteromultimers with each other, but not with other TRP family members in the mouse brain and hippocampus. In hippocampal neurons from -triple-knockout () mice, lacking any TRPC1-, TRPC4-, or TRPC5-containing channels, action potential-triggered excitatory postsynaptic currents (EPSCs) were significantly reduced, whereas frequency, amplitude, and kinetics of quantal miniature EPSC signaling remained unchanged. Likewise, evoked postsynaptic responses in hippocampal slice recordings and transient potentiation after tetanic stimulation were decreased. , mice displayed impaired cross-frequency coupling in hippocampal networks and deficits in spatial working memory, while spatial reference memory was unaltered. animals also exhibited deficiencies in adapting to a new challenge in a relearning task. Our results indicate the contribution of heteromultimeric channels from TRPC1, TRPC4, and TRPC5 subunits to the regulation of mechanisms underlying spatial working memory and flexible relearning by facilitating proper synaptic transmission in hippocampal neurons.
典型瞬时受体电位（TRPC）通道影响多种神经元功能。我们使用定量高分辨率质谱法证明，TRPC1、TRPC4和TRPC5在小鼠大脑和海马体中彼此组装成异源多聚体，但不与其他TRP家族成员组装。在缺乏任何含TRPC1、TRPC4或TRPC5通道的三重敲除（）小鼠的海马神经元中，动作电位触发的兴奋性突触后电流（EPSCs）显著减少，而量子微型EPSC信号的频率、幅度和动力学保持不变。同样，海马切片记录中的诱发突触后反应和强直刺激后的瞬时增强也减少。，小鼠在海马网络中表现出跨频率耦合受损和空间工作记忆缺陷，而空间参考记忆未改变。动物在重新学习任务中适应新挑战时也表现出缺陷。我们的结果表明，TRPC1、TRPC4和TRPC5亚基的异源多聚体通道通过促进海马神经元中适当的突触传递，对空间工作记忆和灵活重新学习的潜在机制调节做出了贡献。
