Microglia are the resident immune cells of the central nervous system. They constantly survey the brain parenchyma for redundant synapses, debris, or dying cells, which they remove through phagocytosis. Microglial ramification, motility, and cytokine release are regulated by tonically active THIK-1 K⁺ channels on the microglial plasma membrane. Here, we examined whether these channels also play a role in phagocytosis. Using pharmacological blockers and THIK-1 knockout (KO) mice, we found that a lack of THIK-1 activity approximately halved both microglial phagocytosis and marker levels for the lysosomes that degrade phagocytically removed material. These changes may reflect a decrease of intracellular [Ca²⁺]_i activity, which was observed when THIK-1 activity was reduced, since buffering [Ca²⁺]_i reduced phagocytosis. Less phagocytosis is expected to result in impaired pruning of synapses. In the hippocampus, mice lacking THIK-1 expression had an increased number of anatomically and electrophysiologically defined glutamatergic synapses during development. This resulted from an increased number of presynaptic terminals, caused by impaired removal by THIK-1 KO microglia. The dependence of synapse number on THIK-1 K⁺ channels, which control microglial surveillance and phagocytic ability, implies that changes in the THIK-1 expression level in disease states may contribute to altering neural circuit function.

小胶质细胞是中枢神经系统的常驻免疫细胞。他们不断地检查脑实质中是否有多余的突触、碎片或垂死的细胞，然后通过吞噬作用将其去除。小胶质细胞的分支、运动和细胞因子释放受小胶质细胞质膜上的强直活性 THIK-1 K ⁺通道的调节。在这里，我们检查了这些通道是否也在吞噬作用中起作用。使用药理学阻滞剂和 THIK-1 敲除 (KO) 小鼠，我们发现缺乏 THIK-1 活性大约使小胶质细胞吞噬作用和降解吞噬去除材料的溶酶体的标志物水平减半。这些变化可能反映了细胞内 [Ca ²⁺ ] _{i的减少。}当 THIK-1 活性降低时观察到活性，因为缓冲 [Ca ²⁺ ] _i降低了吞噬作用。预计较少的吞噬作用会导致突触的修剪受损。在海马体中，缺乏 THIK-1 表达的小鼠在发育过程中具有更多的解剖学和电生理学定义的谷氨酸能突触。这是由于 THIK-1 KO 小胶质细胞的去除受损引起的突触前末端数量增加所致。突触数量对控制小胶质细胞监视和吞噬能力的 THIK-1 K ⁺通道的依赖性意味着疾病状态下 THIK-1 表达水平的变化可能有助于改变神经回路功能。