KCNQ (Kv7) potassium voltage-gated channels are expressed in the dorsal root ganglion (DRG) sensory neurons where they play an important role in controlling DRG neuron excitability. Therefore, any substance modulating the activity of these channels could significantly affect the thresholds and firing rates of DRG neurons, including nociceptors. KCNQ channels are potently augmented by reactive oxygen species, therefore, here we investigated potential effects on KCNQ currents of two redox-related compounds, ascorbate and zinc. Potassium currents were measured in CHO cells overexpressing KCNQ4 subunit, using perforated patch clamp technique. Extracellular perfusion of ascorbate increases KCNQ4 currents by 1.96±0.27. This effect was completely reverted by DTT (0.90±0.29), but not by the Zn chelator TPEN. The removal of the redox-sensitive cysteine cluster in the S2-S3 linker (KCNQ4CCC156-158AAA) completely abolished the ascorbate effect. Application of extracellular ZnCl2 (1-100 μM) was without an effect on KCNQ4 currents while inclusion of 10 μM ZnCl2 in the pipette solution increased the KCNQ4 current amplitude from 536±135 pA to 927±177 pA. Extracellular perfusion of zinc ionophore zinc pyrithione (ZnPy) increased the intracellular concentration of Zinc, as shown with FluoZin3 imaging in HEK cells. Additionally, ZnPy increased the KCNQ4 currents by 2.40±0.40 fold, similarly ZnPy also significantly augmented KCNQ2/3 currents. This increase was completely reverted by TPEN (0.89±0.18) but not by DTT. The increase of KCNQ4 currents by ZnPy was identical between the wild-type and the KCNQ4CCC156-158AAA mutant channel. Taken together, these results suggest that both extracellular ascorbate and intracellular Zn can increase KCNQ currents via distinct mechanisms.