TRPM4 调节颞叶癫痫中的门区苔藓细胞丢失。

TRPM4 regulates hilar mossy cell loss in temporal lobe epilepsy.

机构信息

Institute of Physiology, Medical School, University of Pécs, Pécs, 7624, Hungary.

Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, 7624, Hungary.

出版信息

BMC Biol. 2023 Apr 26;21(1):96. doi: 10.1186/s12915-023-01604-3.

BACKGROUND

Mossy cells comprise a large fraction of excitatory neurons in the hippocampal dentate gyrus, and their loss is one of the major hallmarks of temporal lobe epilepsy (TLE). The vulnerability of mossy cells in TLE is well known in animal models as well as in patients; however, the mechanisms leading to cellular death is unclear.

RESULTS

Transient receptor potential melastatin 4 (TRPM4) is a Ca-activated non-selective cation channel regulating diverse physiological functions of excitable cells. Here, we identified that TRPM4 is present in hilar mossy cells and regulates their intrinsic electrophysiological properties including spontaneous activity and action potential dynamics. Furthermore, we showed that TRPM4 contributes to mossy cells death following status epilepticus and therefore modulates seizure susceptibility and epilepsy-related memory deficits.

CONCLUSIONS

Our results provide evidence for the role of TRPM4 in MC excitability both in physiological and pathological conditions.

背景

苔藓细胞构成了海马齿状回中兴奋性神经元的很大一部分，其丧失是颞叶癫痫（TLE）的主要标志之一。在动物模型和患者中，TLE 中苔藓细胞的易感性是众所周知的；然而，导致细胞死亡的机制尚不清楚。

结果

瞬时受体电位 melastatin 4（TRPM4）是一种 Ca2+激活的非选择性阳离子通道，调节兴奋细胞的多种生理功能。在这里，我们发现 TRPM4 存在于门区苔藓细胞中，并调节其内在的电生理特性，包括自发性活动和动作电位动力学。此外，我们表明 TRPM4 有助于癫痫持续状态后苔藓细胞的死亡，因此调节癫痫发作的易感性和与癫痫相关的记忆缺陷。