Non-NMDAR neuronal Ca(2+)-permeable channels in delayed neuronal death and as potential therapeutic targets for ischemic brain damage.

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 [Ca(2+)]c and [Zn(2+)]c. A number of Ca(2+)-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 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.

EXPERT OPINION

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.