Activation of metabotropic glutamate receptor 1 regulates hippocampal CA1 region excitability in rats with status epilepticus by suppressing the HCN1 channel  

作　　者：Xiao-Dan Luo Tao Xiang Si-Jun Li Mei-Gang Ma Mei-Ling Chen Yuan Wu 

机构地区：[1]Department of Neurology,First Affiliated Hospital of Guangxi Medical University,Nanning,Guangxi Zhuang Autonomous Region,China [2]Department of Neurology,First Affiliated Hospital of University of South China,Hengyang,Hunan Province,China [3]Department of Neurology,Affiliated Hospital of Guilin Medical University,Guilin,Guangxi Zhuang Autonomous Region,China

出　　处：《Neural Regeneration Research》2023年第3期594-602,共9页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.81760242(to MGM).

摘　　要：Dysregulation of hyperpolarization-activated cyclic nucleotide-gated cation(HCN)channels alters neuronal excitability.However,the role of HCN channels in status epilepticus is not fully understood.In this study,we established rat models of pentylenetetrazole-induced status epilepticus.We performed western blot assays and immunofluorescence staining.Our results showed that HCN1 channel protein expression,particularly HCN1 surface protein,was significantly decreased in the hippocampal CA1 region,whereas the expression of HCN2 channel protein was unchanged.Moreover,metabolic glutamate receptor 1(mGluR1)protein expression was increased after status epilepticus.The mGluR1 agonist(RS)-3,5-dihydroxyphenylglycine injected intracerebroventricularly increased the sensitivity and severity of pentylenetetrazole-induced status epilepticus,whereas application of the mGluR1 antagonist(+)-2-methyl-4-carboxyphenylglycine(LY367385)alleviated the severity of pentylenetetrazole-induced status epilepticus.The results from double immunofluorescence labeling revealed that mGluR1 and HCN1 were co-localized in the CA1 region.Subsequently,a protein kinase A inhibitor(H89)administered intraperitoneally successfully reversed HCN1 channel inhibition,thereby suppressing the severity and prolonging the latency of pentylenetetrazole-induced status epilepticus.Furthermore,H89 reduced the level of mGluR1,downregulated cyclic adenosine monophosphate(cAMP)/protein kinase A expression,significantly increased tetratricopeptide repeat-containing Rab8b-interacting protein(TRIP8b)(1a-4)expression,and restored TRIP8b(1b-2)levels.TRIP8b(1a-4)and TRIP8b(1b-2)are subunits of Rab8b interacting protein that regulate HCN1 surface protein.

关 键 词：(RS)-3 5-dihydroxyphenylglycine CA1 region EXCITABILITY H89 HCN1 channel LY367385 MGLUR1 PENTYLENETETRAZOLE status epilepticus 

分 类 号：R742.1[医药卫生—神经病学与精神病学]