Thapsigargin evokes increased Na⁺ transport in H441 cells and, at least in part, this response is due to a Ca²⁺-dependent increase in K⁺ conductance (G_K) (McNeill et al., 2005). To characterise the channels underlying this response, we have now explored the effects of putative K⁺ channel blockers upon the thapsigargin-evoked increase in membrane current. Ba²⁺ (5 mM) caused 73 ± 8 % inhibition whilst 1 μM clotrimazole essentially abolished the response (97 ± 5 %) and, since apamin (1 μM, n = 4) and iberiotoxin (0.1 μM, n = 7) were ineffective, this suggests that the thapsigargin-evoked increase in G_K (McNeill et al., 2005) reflects increased activity of K⁺ channels belonging to the I_K family. Further evidence of this came from RT-PCR based studies which showed that H441 cells expressed I_K channel mRNA transcripts but did not express either the large or small conductance K⁺ channel. Moreover, 1 mM EBIO, a substance that characteristically activates I_K channels, caused an increased in membrane conductance (control: 353 ± 68 pS cell^-1, EBIO: 1222 ± 245 pS cell ^-1) that reflected activation of a K⁺ selective current and which caused a hyperpolarization of V_m (control: -52 ± 3 mV; EBIO: -79 ± 1 mV, P < 0.001). These data suggest that the thapsigargin-evoked increase in I_SC (McNeill et al., 2005) is due to increased activity of I_K channels, a hypothesis that predicts that EBIO-evoked activation of these channels will mimic the electrometric response to thapsigargin. We therefore explored the effects of EBIO upon I_SC and [Ca²⁺]_i measured simultaneously in polarised H441 cells (Fig 1). As anticipated, EBIO increased I_SC without affecting [Ca²⁺]_i and so the present data suggest that Ca²⁺ mobilising agonists could be important regulators of epithelial Na⁺ transport in some tissues.