TRPM7 Channels as Potential Therapeutic Targets for Stroke

Abstract

Transient receptor potential melastatin 7 (TRPM7) channels are calcium-permeable nonselective cation channels. TRPM7 channels are widely expressed in different tissues including the brain and are thought to regulate calcium homeostasis based on the metabolic state of the cell. TRPM7 partakes in a wide range of processes in cell biology that affects cell adhesion, cell growth, and proliferation, as well as in skeleton formation and embryonic development. TRPM7 plays a key role in brain damages and neuronal cell death in ischemia and hypoxia. As one of the key components of the nonglutamate mechanism of stroke besides the traditional glutamate mechanism that initiates the excitotoxicity, TRPM7 also triggers the intracellular ionic imbalance and neuronal cell death in anoxia in vitro and ischemia in vivo, respectively. We have shown that TRPM7 channels, expressed in adult hippocampal and cortical neurons, triggered neuronal cell death under ischemic conditions, and gene silencing of TRPM7 with siRNA increased neuronal survival and improved neurobehavioral outcomes to cerebral ischemia in vivo. Recently, we also showed that TRPM7 plays a neuroprotective role in brain damage to hypoxia in vivo. We have demonstrated the contributions of TRPM7 channels in many processes in both physiology and pathophysiology, as well as the current understanding of the role of TRPM7 in stroke.