Hydrogen sulfide induced disruption of Na+ homeostasis in the cortex

Maintenance of ionic balance is essential for neuronal functioning. Hydrogen sulfide (H(2)S), a known toxic environmental gaseous pollutant, has been recently recognized as a gasotransmitter involved in numerous biological processes, and is believed to play an important role in the neural activities under both physiological and pathological conditions. However, it is unclear if it plays any role in maintenance of ionic homeostasis in the brain under physiological/pathophysiolocal conditions. Here we report by directly measuring Na(+) activity using Na(+) selective electrodes in mouse cortical slices that H(2)S donor sodium hydrosulfide (NaHS) increased Na(+) influx in a concentration-dependent manner. This effect could be partially blocked by either Na(+) channel blocker or NMDA receptor blocker alone or almost completely abolished by co-application of both blockers, but not by non-NMDA receptor blocker. These data suggest that increased H(2)S in pathophysiological conditions, e.g., hypoxia/ischemia, potentially cause a disruption of ionic homeostasis by massive Na(+) influx through Na(+) channels and NMDA receptors, thus injuring neural functions. Activation of delta-opioid receptors (DOR), which reduces Na(+) currents/influx in normaxia, had no effect on H(2)S-induced Na(+) influx, suggesting that H(2)S-induced disruption of Na(+) homeostasis is resistant to DOR regulation and may play a major role in neuronal injury in pathophysiological conditions, e.g., hypoxia/ischemia.