Dexamethasone-treated H441 bronchial epithelial cells spontaneously generate amiloride-sensitive I_SC attributable to expression of the epithelial Na⁺ channel subunits (α-, β-and λ-ENaC) and a consequential rise in amiloride-sensitive apical conductance (G_amil) (Sayegh et al. 1999). However, these subunits can form a range of Na⁺ channel isoforms that differ in their relative conductances to Na⁺ and K⁺ (Jain et al. 2001). It is therefore impossible to infer the conductive properties of the channels underlying this response and so we now explore the conductive properties of the apical membrane in dexamethasone-treated H441 cells.

Under hormone-free conditions only ~50 % of cultures formed resistive epithelia (344 ± 86 V cm², mean ± S.E.M.) and these generated very little I_SC (1.3 ± 0.6 µA cm^-2). However, dexamethsaone-treated (0.2 µM) cells consistently grew into coherent epithelial sheets (586 ± 47 V cm²) that generated substantial currents (21.5 ± 2.3 µA cm^-2) (see also Sayegh et al. 1999). This hormone had no effect upon the current due to Na⁺ pump activity (control: 40.8 ± 7.8 µAcm^-2; dexamethasone-treated: 34.3 ± 3.8 µAcm^-2), which was estimated as described by Baines et al. (2001), and so this response must reflect an effect on the apical membrane. Examination of apical membrane currents showed that inwardly directed Na⁺ gradients caused a rightward shift in V_rev (Fig. 1) and analysis of these data indicated that G_amil was 4.2-fold more permeable to Na⁺ than to K⁺. The increase in I_SC can thus be attributed to the induction of a selective, apical Na⁺ conductance.

This work was supported by the Wellcome Trust.