Biomedicum Helsinki, Institute of Biomedicine/Physiology, University of Helsinki, Finland.
Cell Calcium. 2010 Aug-Sep;48(2-3):114-23. doi: 10.1016/j.ceca.2010.07.005. Epub 2010 Aug 21.
TRPC channels play significant roles in the regulation of neuronal plasticity and development. The mechanism by which these nonselective cation channels exert their trophic actions appears to involve entry of Ca(2+) into the cells. Using a neuronal cell model (differentiated human IMR32 neuroblastoma cells), we demonstrate a central role for sodium entry via TRPC3/6 channels in receptor-mediated increases in intracellular calcium. These Na(+)-dependent Ca(2+) influxes, which were observed in a subpopulation of cells, were efficiently blocked by protein kinase C activation, by the Na(+)/Ca(2+) exchanger inhibitors, and by molecular disruption of TRPC3/6 channel function. On the other hand, another subpopulation of cells showed a Na(+)-independent Ca(2+) entry upon stimulation of the same receptors, orexin/hypocretin and bradykinin receptors. This second type of response was not affected by the above mentioned treatments, but it was sensitive to polyvalent cations, such as ruthenium red, spermine and Gd(3+). The data suggest that a NCX-TRPC channel interaction constitutes an important functional unit in receptor-mediated Ca(2+) influx in neuronal cells.
TRPC 通道在神经元可塑性和发育的调节中发挥重要作用。这些非选择性阳离子通道发挥营养作用的机制似乎涉及 Ca(2+)进入细胞。使用神经元细胞模型（分化的人 IMR32 神经母细胞瘤细胞），我们证明了 TRPC3/6 通道通过钠内流在受体介导的细胞内钙增加中起核心作用。这些在细胞亚群中观察到的 Na(+)-依赖性 Ca(2+)内流可被蛋白激酶 C 激活、Na(+)/Ca(2+)交换抑制剂和 TRPC3/6 通道功能的分子破坏有效地阻断。另一方面，刺激相同受体（orexin/hypocretin 和缓激肽受体）时，另一亚群细胞表现出 Na(+)非依赖性 Ca(2+)内流。这种第二种类型的反应不受上述处理的影响，但对多价阳离子（如钌红、精胺和 Gd(3+)）敏感。数据表明，NCX-TRPC 通道相互作用构成了神经元细胞中受体介导的 Ca(2+)内流的重要功能单元。
