DRG neurons were freshly isolated from rats and the neurons were incubated for 24 h with buthionine sulfoximine (BSO). In whole-cell patch clamp experiments, TRPM2 currents in the DRG incubated with BSO were gated by H2O2. TRPM2 channels current densities, cytosolic free Ca2+ content, and lipid peroxidation values in the neurons were higher in H2O2 and BSO + H2O2 group than in controls; however GSH and GSH peroxidase (GSH-Px) values were decreased. BSO + H2O2-induced TRPM2 channel gating was totally inhibited by extracellular NAC and partially inhibited by 2-aminoethyl diphenylborinate. GSH-Px activity, lipid peroxidation and GSH levels in the DRG neurons were also modulated by NAC.
In conclusion, we observed a modulator role of NAC on Ca2+ influx through a TRPM2 channel in intracellular GSH depleted DRG neurons. NAC incubation before BSO exposure appears to be more protective than NAC incubation after BSO exposure. Since cytosolic thiol group depletion is a common feature of neuropathic pain, our findings are relevant to the etiology and treatment of pain neuropathology in DRG neurons.