NCX and EAAT transporters in ischemia: At the crossroad between glutamate metabolism and cell survival

Energy metabolism impairment is a central event in the pathophysiology of ischemia. The limited availability of glucose and oxygen strongly affects mitochondrial activity, thus leading to ATP depletion. In this setting, the switch to alternative energy sources could ameliorate cells survival by enhancing ATP production, thus representing an attractive strategy for ischemic treatment. In this regard, some studies have recently re-evaluated the metabolic role of glutamate and its potential to promote cell survival under pathological conditions. In the present review, we discuss the ability of glutamate to exert an “energizing role” in cardiac and neuronal models of hypoxia/reoxygenation (H/R) injury, focusing on the Na⁺/Ca²⁺ exchanger (NCX) and the Na⁺-dependent excitatory amino acid transporters (EAATs) as key players in this metabolic pathway.