Hartmann Jana, Dragicevic Elena, Adelsberger Helmuth, Henning Horst A, Sumser Martin, Abramowitz Joel, Blum Robert, Dietrich Alexander, Freichel Marc, Flockerzi Veit, Birnbaumer Lutz, Konnerth Arthur
Institute of Neuroscience and Center for Integrated Protein Science, Technical University Munich, 80802 Munich, Germany.
Neuron. 2008 Aug 14;59(3):392-8. doi: 10.1016/j.neuron.2008.06.009.
In the mammalian central nervous system, slow synaptic excitation involves the activation of metabotropic glutamate receptors (mGluRs). It has been proposed that C1-type transient receptor potential (TRPC1) channels underlie this synaptic excitation, but our analysis of TRPC1-deficient mice does not support this hypothesis. Here, we show unambiguously that it is TRPC3 that is needed for mGluR-dependent synaptic signaling in mouse cerebellar Purkinje cells. TRPC3 is the most abundantly expressed TRPC subunit in Purkinje cells. In mutant mice lacking TRPC3, both slow synaptic potentials and mGluR-mediated inward currents are completely absent, while the synaptically mediated Ca2+ release signals from intracellular stores are unchanged. Importantly, TRPC3 knockout mice exhibit an impaired walking behavior. Taken together, our results establish TRPC3 as a new type of postsynaptic channel that mediates mGluR-dependent synaptic transmission in cerebellar Purkinje cells and is crucial for motor coordination.
在哺乳动物中枢神经系统中，缓慢的突触兴奋涉及代谢型谷氨酸受体（mGluRs）的激活。有人提出，C1型瞬时受体电位（TRPC1）通道是这种突触兴奋的基础，但我们对TRPC1基因敲除小鼠的分析并不支持这一假说。在此，我们明确表明，小鼠小脑浦肯野细胞中mGluR依赖的突触信号传导需要TRPC3。TRPC3是浦肯野细胞中表达最丰富的TRPC亚基。在缺乏TRPC3的突变小鼠中，缓慢的突触电位和mGluR介导的内向电流完全缺失，而细胞内储存库中突触介导的Ca2+释放信号则未改变。重要的是，TRPC3基因敲除小鼠表现出行走行为受损。综上所述，我们的结果确立了TRPC3作为一种新型的突触后通道，它介导小脑浦肯野细胞中mGluR依赖的突触传递，并且对运动协调至关重要。
