Epithelial Na+ absorption is dependent upon K+ channels that stabilise Vm and, whilst Na+ -absorbing H441 human airway epithelial cells express K+ channels belonging to the KCNN4 family, these cannot contribute to basal Na+ transport since they are inactive at resting [Ca2+ ]i (SM Wilson et al. Am. J. Physiol. - Lung Cell. Mol. Physiol. 291:L957-L965, 2006). We have therefore used the perforated patch technique to characterise the K+ channels underlying resting GK in these cells. At 10 mM [Na+ ]o (NMDG+ substitution, n = 6), raising [K+ ]o from 5 mM to 134.5 mM depolarized Vm from -60.4 ± 2.8 mV to -33.5 ± 7.6 mV(P < 0.001). Whilst this depolarization confirms that GK, is significant, GCl must also be substantial as Vm did not depolarise to EK but lay between EK and ECl . Ba2+ (5 mM) had no effect upon the currents recorded at high [K+ ]o whereas 3 mM bupivicaine reduced total conductance from 0.89 ± 0.12 pS cell-1 to 0.38 ± 0.35 pS cell-1 (P < 0.01). Further analysis showed that VRev for the bupivicaine-sensitive current lay at a potential close to EK (~0 mV). This potential was unaffected by lowering [Cl-]o to 21 mM (gluconate substitution) whereas reducing [K+ ]o to 20 mM, and thus moving EK to -43 mV, hyperpolarized VRev to -37.6 ± 5.4 mV. The bubivicaine-sensitive current is thus K+ - selective and so ~50% of the current recorded at high [K+ ]o flows through channels blocked by bupivicaine but not Ba2+ .