Calcium-permeable ion channels involved in glutamate receptor-independent ischemic brain injury

Abstract

Brain ischemia is a leading cause of death and long-term disabilities worldwide. Unfortunately, current treatment is limited to thrombolysis, which has limited success and a potential side effect of intracerebral hemorrhage. Searching for new cell injury mechanisms and therapeutic interventions has become a major challenge in the field. It has been recognized for many years that intracellular Ca(2+) overload in neurons is essential for neuronal injury associated with brain ischemia. However, the exact pathway(s) underlying the toxic Ca(2+) loading remained elusive. This review discusses the role of two Ca(2+)-permeable cation channels, TRPM7 and acid-sensing channels, in glutamate-independent Ca(2+) toxicity associated with brain ischemia.

Figure 1

Potential pathways responsible for intracellular Ca²⁺ accumulation in neurons in ischemic condition. VGCC: voltage-gated Ca²⁺ channel; ASIC: acid-sensing ion channel; ROS: reactive oxygen species; TRPM7: transient receptor potential melastatin 7; Na⁺/Ca²⁺: sodium-calcium exchanger.