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

• Published in: Neurochemistry international Vol. 150; p. 105155
• Main Authors: Xiao, Fuyao, Zhang, Xiaojie, Ni, Pinfei, Yu, Haibo, Gao, Qiming, Li, Mengyao, Huo, Peiyun, Wei, Ziwei, Wang, Sihan, Zhang, Yi, Zhao, Rui, Li, Aixue, Li, Zhirui, Li, Yuejia, Cheng, Haixiao, Du, Libo, Ren, Suping, Yu, Qun, Liu, Yang, Zhao, Yuming
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2021
• Subjects: Animals; Brain Ischemia - genetics; Brain Ischemia - metabolism; Brain Ischemia - prevention & control; Cell Line, Transformed; Ischemic Stroke - genetics; Ischemic Stroke - metabolism; Ischemic Stroke - prevention & control; Kv4.2; Male; Maze Learning - physiology; Mice; Mice, Inbred C57BL; Neural differentiation; Neurogenesis; Neurogenesis - physiology; Shal Potassium Channels - analysis; Shal Potassium Channels - biosynthesis; Shal Potassium Channels - genetics; Stroke; Voltage-dependent potassium channels; Stroke; Kv4.2; Neural differentiation; Voltage-dependent potassium channels; Neurogenesis
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2021.105155

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. [Display omitted] •Voltage-dependent potassium channel Kv4.2 promote neurogenesis.