Non-NMDAR neuronal Ca(2+)-permeable channels in delayed neuronal death and as potential therapeutic targets for ischemic brain damage.
BACKGROUND
Transient cerebral ischemia represents the most common cause of complex chronic disability in adults due to delayed neuronal death as a result of aberrant post-ischemic increases in the [Ca(2+)]c and [Zn(2+)]c. A number of Ca(2+)-permeable channels are engaged in transient ischemia-induced neuronal death.


METHODS
In this review, the authors discuss the GluA2-lacking AMPARs, acid-sensing ion channel 1a, melastatin-related transient receptor potential 2 (TRPM2), TRPM7 and store-operated Ca(2+) channels expressed in ischemia-vulnerable neurons, and focus on the studies using in vitro and in vivo models of transient ischemia that supports a significant role for these channels in inducing increases in the [Ca(2+)]c and/or [Zn(2+)]c and delayed neuronal death, and their potential as therapeutic targets.


CONCLUSIONS
Non-NMDAR Ca(2+)-permeable channels are important mechanisms mediating delayed neuronal death and cognitive dysfunctions after transient ischemia. Identification of such Ca(2+)-permeable channels significantly improves our understanding of the molecular events leading to ischemic brain damage and provides promising novel targets for post-ischemic therapeutics treating ischemic brain damage.
Xinxiang Medical University, School of Basic Medical Sciences, Department of Physiology and Neurobiology , Xinxiang , China.
Chaokun
C
Li
Li
L
Meng
Xin
X
Li
Dongliang
D
Li
Lin-Hua
LH
Jiang
D000328:Adult; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000503:physiopathology; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009474:Neurons / Q000473:pathology*; D015032:Zinc / Q000378:metabolism
D015032:Zinc; D002118:Calcium
AMPARs; Ca2+; Zn2+; acid-sensing ion channel 1a; delayed neuronal death; melastatin-related transient receptor potential 2; melastatin-related transient receptor potential 7; store-operated Ca2+ channels; transient ischemia