Role of TRPM7 in cerebral ischaemia and hypoxia.

Transient receptor potential melastatin 7 (TRPM7) channel, a calcium-permeable non-selective divalent cation channel, is broadly expressed in various cells and tissues, including the brain. TRPM7 is thought to be coupled to the metabolic state and regulate calcium homeostasis in the cell. TRPM7 takes part in a wide range of cell biology processes that affect cell growth and proliferation, as well as in embryonic development and skeleton formation. TRPM7 plays a significant role in ischaemic and hypoxic brain injury and neuronal cell death. TRPM7, as a key non-glutamate mechanism of cerebral ischaemia, also triggers an intracellular ionic imbalance and neuronal cell death in ischaemia and hypoxia. We have reported that TRPM7 is expressed in neurons of the hippocampus and cortex and activation of TRPM7 induced ischaemic neuronal cell death; suppression of TRPM7 with virally mediated gene silencing using siRNA reduced ischaemic neuronal cell death and improved neurobehavioural outcomes in vivo. Recently, we also demonstrated that inhibition of TRPM7 using pharmacological means promoted neuronal outgrowth in vitro and provided neuroprotection against brain injury to hypoxia in vivo. Thus, we have shown the contributions of TRPM7 in many physiological and pathophysiological processes, including hypoxia and ischaemia.