Rapid downregulation of NCX and PMCA in hippocampal neurons following H₂O₂ oxidative stress

Na⁺/Ca²⁺ exchangers (NCXs) and plasma membrane Ca²⁺ pumps (PMCAs) are crucial for intracellular Ca²⁺ homeostasis and Ca²⁺ signaling. Elevated [Ca²⁺] _i is a hallmark of neurodegenerative disease and stroke. Here we studied the short-term effect of oxidative stress on the plasma membrane Ca ²⁺ extrusion systems in hippocampal neurons (HN) and found that after 2-3 h exposure to 300 μM H₂O₂, all NCXs and PMCAs were significantly downregulated at the RNA (NCX) and protein (PMCA) level. Rapid internalization and aggregation of the PMCA was also observed. Our data show that the plasma membrane calcium extrusion systems are sensitive early targets of neurotoxic oxidative stress.