2. Academic Validation
  3. Voltage-dependent potassium channel Kv4.2 alleviates the ischemic stroke impairments through activating neurogenesis

Voltage-dependent potassium channel Kv4.2 alleviates the ischemic stroke impairments through activating neurogenesis

  • Neurochem Int. 2021 Nov;150:105155. doi: 10.1016/j.neuint.2021.105155.
Fuyao Xiao 1,  Xiaojie Zhang 2,  Pinfei Ni 1,  Haibo Yu 3,  Qiming Gao 4,  Mengyao Li 1,  Peiyun Huo 4,  Ziwei Wei 1,  Sihan Wang 4,  Yi Zhang 1,  Rui Zhao 1,  Aixue Li 1,  Zhirui Li 4,  Yuejia Li 4,  Haixiao Cheng 4,  Libo Du 2,  Suping Ren 5,  Qun Yu 5,  Yang Liu 2,  Yuming Zhao 6
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Basic Medical Science, Capital Medical University, Beijing, PR China; Department of Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, PR China.
  • 2 State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, PR China.
  • 3 State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, PR China.
  • 4 Department of Pharmacology, School of Basic Medical Science, Capital Medical University, Beijing, PR China.
  • 5 Beijing Institute of Transfusion Medicine, Beijing, 100850, PR China.
  • 6 Department of Pharmacology, School of Basic Medical Science, Capital Medical University, Beijing, PR China. Electronic address: yumingzhao@ccmu.edu.cn.
PMID: 34384853 DOI: 10.1016/j.neuint.2021.105155
Abstract

As well as their ion transportation function, the voltage-dependent potassium channels could act as the cell signal inducer in a variety of pathogenic processes. However, their roles in neurogenesis after stroke insults have not been clearly illustrated. In our preliminary study, the expressions of voltage-dependent potassium channels Kv4.2 was significantly decreased after stroke in cortex, striatum and hippocampus by real-time quantitative PCR assay. To underlie the neuroprotection of Kv4.2 in stroke rehabilitation, recombinant plasmids encoding the cDNAs of mouse Kv4.2 was constructed. Behavioral tests showed that the increased Kv4.2 could be beneficial to the recovery of the sensory, the motor functions and the cognitive deficits after stroke. Temozolomide (TMZ), an inhibitor of neurogenesis, could partially abolish the mentioned protections of Kv4.2. The immunocytochemical staining showed that Kv4.2 could promote the proliferations of neural stem cells and induce the neural stem cells to differentiate into neurons in vitro and in vivo. And Kv4.2 could up-regulate the expressions of ERK1/2, p-ERK1/2, p-STAT3, NGF, p-TrkA, and BDNF, CAMKII and the concentration of intracellular CA2+. Namely, we concluded that Kv4.2 promoted neurogenesis through ERK1/2/STAT3, NGF/TrkA, CA2+/CAMKII signal pathways and rescued the ischemic impairments. Kv4.2 might be a potential drug target for ischemic stroke intervention.

Keywords

Kv4.2; Neural differentiation; Neurogenesis; Stroke; Voltage-dependent potassium channels.

Figures
Products