Institute of Synaptic Physiology, ZMNH, University Medical Center Hamburg-Eppendorf, Falkenried, 94 20251, Hamburg, Germany.
Department of Psychological and Brain Sciences, Boston University, Boston, USA.
Sci Rep. 2022 Apr 9;12(1):6000. doi: 10.1038/s41598-022-09875-6.
The transient receptor potential melastatin 4 (TRPM4) channel contributes to disease severity in the murine experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis and to neuronal cell death in models of excitotoxicity and traumatic brain injury. As TRPM4 is activated by intracellular calcium and conducts monovalent cations, we hypothesized that TRPM4 may contribute to and boost excitatory synaptic transmission in CA1 pyramidal neurons of the hippocampus. Using single-spine calcium imaging and electrophysiology, we found no effect of the TRPM4 antagonists 9-phenanthrol and glibenclamide on synaptic transmission in hippocampal slices from healthy mice. In contrast, glibenclamide but not 9-phenanthrol reduced excitatory synaptic potentials in slices from EAE mice, an effect that was absent in slices from EAE mice lacking TRPM4. We conclude that TRPM4 plays little role in basal hippocampal synaptic transmission, but a glibenclamide-sensitive TRPM4-mediated contribution to excitatory postsynaptic responses is upregulated at the acute phase of EAE.
瞬时受体电位 melastatin 4（TRPM4）通道有助于多发性硬化症的实验性自身免疫性脑脊髓炎（EAE）模型中的疾病严重程度，并有助于兴奋性毒性和创伤性脑损伤模型中的神经元细胞死亡。由于 TRPM4 被细胞内钙激活并传导单价阳离子，我们假设 TRPM4 可能有助于增强海马 CA1 锥体神经元中的兴奋性突触传递。使用单棘突钙成像和电生理学，我们发现 TRPM4 拮抗剂 9-菲咯啉和格列本脲对健康小鼠海马切片中的突触传递没有影响。相比之下，格列本脲而不是 9-菲咯啉降低了 EAE 小鼠切片中的兴奋性突触电位，而在缺乏 TRPM4 的 EAE 小鼠切片中则没有这种作用。我们得出的结论是，TRPM4 在基础海马突触传递中作用不大，但在 EAE 的急性期，一种格列本脲敏感的 TRPM4 介导的对兴奋性突触后反应的贡献被上调。
