PubMed 25429618

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPM , TRPM2

Title: TRPM2 channel deficiency prevents delayed cytosolic Zn2+ accumulation and CA1 pyramidal neuronal death after transient global ischemia.

Authors: M Ye, W Yang, J F Ainscough, X-P Hu, X Li, A Sedo, X-H Zhang, X Zhang, Z Chen, X-M Li, D J Beech, A Sivaprasadarao, J-H Luo, L-H Jiang

Journal, date & volume: Cell Death Dis, 2014 , 5, e1541

PubMed link:

Transient ischemia is a leading cause of cognitive dysfunction. Postischemic ROS generation and an increase in the cytosolic Zn(2+) level ([Zn(2+)]c) are critical in delayed CA1 pyramidal neuronal death, but the underlying mechanisms are not fully understood. Here we investigated the role of ROS-sensitive TRPM2 (transient receptor potential melastatin-related 2) channel. Using in vivo and in vitro models of ischemia-reperfusion, we showed that genetic knockout of TRPM2 strongly prohibited the delayed increase in the [Zn(2+)]c, ROS generation, CA1 pyramidal neuronal death and postischemic memory impairment. Time-lapse imaging revealed that TRPM2 deficiency had no effect on the ischemia-induced increase in the [Zn(2+)]c but abolished the cytosolic Zn(2+) accumulation during reperfusion as well as ROS-elicited increases in the [Zn(2+)]c. These results provide the first evidence to show a critical role for TRPM2 channel activation during reperfusion in the delayed increase in the [Zn(2+)]c and CA1 pyramidal neuronal death and identify TRPM2 as a key molecule signaling ROS generation to postischemic brain injury.