Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago, Chile.
Mol Brain. 2024 Sep 12;17(1):66. doi: 10.1186/s13041-024-01140-3.
TRPM4 is a non-selective cation channel activated by intracellular Ca but only permeable to monovalent cations, its activation regulates membrane potential and intracellular calcium. This channel participates in the migration and adhesion of non-excitable cells and forms an integral part of the focal adhesion complex. In neurons, TRPM4 expression starts before birth and its function at this stage is not clear, but it may function in processes such as neurite development. Here we investigate the role of TRPM4 in neuritogenesis. We found that neurons at DIV 0 express TRPM4, the inhibition of TRPM4 using 9-Ph reduces neurite number and slows the progression of neurite development, keeping neurons in stage 1. The genetic suppression of TRPM4 using an shRNA at later stages (DIV2) reduces neurite length. Conversely, at DIV 0, TRPM4 inhibition augments the Cch-induced Ca increase, altering the calcium homeostasis. Together, these results show that TRPM4 participates in progression of neurite development and suggest a critical role of the calcium modulation during this stage of neuronal development.
TRPM4 是一种非选择性阳离子通道，被细胞内 Ca 激活，但仅对单价阳离子具有通透性，其激活调节膜电位和细胞内钙。该通道参与非兴奋性细胞的迁移和黏附，并形成粘着斑复合物的一个组成部分。在神经元中，TRPM4 的表达在出生前就开始了，但其在这一阶段的功能尚不清楚，但它可能在神经突发育等过程中发挥作用。在这里，我们研究了 TRPM4 在神经突生成中的作用。我们发现，在 DIV0 时神经元表达 TRPM4，使用 9-Ph 抑制 TRPM4 会减少神经突数量并减缓神经突发育的进程，使神经元停留在 1 期。在后期（DIV2）使用 shRNA 抑制 TRPM4 会减少神经突长度。相反，在 DIV0 时，TRPM4 抑制增强了 Cch 诱导的 Ca 增加，改变了钙稳态。总之，这些结果表明 TRPM4 参与了神经突发育的进展，并表明在神经元发育的这一阶段钙调节起着关键作用。
