Non-NMDAR neuronal Ca²⁺–permeable channels in delayed neuronal death and as potential therapeutic targets for ischemic brain damage

Abstract

Introduction: 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 [Ca²⁺]_c and [Zn²⁺]_c. A number of Ca²⁺-permeable channels are engaged in transient ischemia-induced neuronal death.

Areas covered: 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 Ca²⁺ 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 [Ca²⁺]_c and/or [Zn²⁺]_c and delayed neuronal death, and their potential as therapeutic targets.

Expert opinion: Non-NMDAR Ca²⁺-permeable channels are important mechanisms mediating delayed neuronal death and cognitive dysfunctions after transient ischemia. Identification of such Ca²⁺-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.

Keywords:

• AMPARs
• acid-sensing ion channel 1a
• Ca²⁺
• delayed neuronal death
• transient ischemia
• melastatin-related transient receptor potential 2
• melastatin-related transient receptor potential 7
• store-operated Ca2+ channels
• transient ischemia
• Zn²⁺

Acknowledgment

L Meng and X Li contributed equally to this work.

Declaration of interest

The work was supported in part by Xinxiang Medical University start-up founding (C Li and L-H Jiang), Natural Science Foundation of China (grant No.31471118 to L-H J). X Li is a recipient of University of Leeds-Chinese Scholar Council Scholarship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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