Pulmonary neuroepithelial bodies (NEB) form innervated cell clusters that express voltage-activated currents and function as airway O2 sensors. We investigated A-type K+ currents in NEB cells using neonatal rabbit lung slice preparation. The whole cell K+ current was slowly inactivating with activation threshold of ∼−30 mV. This current was blocked ∼27% by blood-depressing substance I (BDS-I; 3 μM), a selective blocker of Kv3.4 subunit, and reduced ∼20% by tetraethylammonium (TEA; 100 μM). The BDS-I-sensitive component had an average peak value of 189 ± 14 pA and showed fast inactivation kinetics that could be fitted by one-component exponential function with a time constant of (τ1) 77 ± 10 ms. This Kv slowly inactivating current was also blocked by heteropodatoxin-2 (HpTx-2; 0.2 μM), a blocker of Kv4 subunit. The HpTx-2-sensitive current had an average peak value of 234 ± 23 pA with a time constant (τ) 82 ± 11 ms. Hypoxia (Po2 = 15–20 mmHg) inhibited the slowly inactivating K+ current by ∼47%, during voltage steps from −30 to +30 mV, and no further inhibition occurred when TEA was combined with hypoxia. Nicotine at concentrations of 50 and 100 μM suppressed the slowly inactivating K+ current by ∼24 and ∼40%, respectively. This suppression was not reversed by mecamylamine suggesting a direct effect of nicotine on these K+ channels. In situ hybridization experiments detected expression of mRNAs for Kv3.4 and Kv4.3 subunits, while double-label immunofluorescence confirmed membrane localization of respective channel proteins in NEB cells. These studies suggest that the hypoxia-sensitive current in NEB cells is carried by slowly inactivating A-type K+ channels, which underlie their oxygen-sensitive potassium currents, and that exposure to nicotine may directly affect their function, contributing to smoking-related lung disease.