The effects of 1-EBIO, DC-EBIO and riluzole (RLZ) on vectorial epithelial Na⁺ transport were investigated by measuring short-circuit currents (I_SC , mA/cm ² ± SD) of rat fetal (E19) distal lung epithelial monolayers in Ussing chambers. 1-EBIO and DC-EBIO increased I_SC (EC₅₀ = 1.0 ± 0.2 mM and 42 ± 5 mM, respectively), while RLZ had only a transient inhibitory effect. Amiloride (I_Amil control 3.1 ± 0.9) and Ouabain (I_Ouab control

3.5 ± 0.9) sensitive I_SC were increased (p<0.05) by 3 mM 1EBIO (I_Amil 5.0 ± 0.8 & I_Ouab 5.5 ± 0.7), but not by 0.3 mM RLZ (I_Amil 2.4 ± 0.7 & I_Ouab 3.1 ± 0.8). TRAM-34 (1mM) blocked basal and DC-EBIO (0.1 mM) elicited I_SC. The amiloride sensitive Na⁺ current of the apical membrane was measured using a Na⁺ gradient (133:5, apical to basolateral) after basolateral permeabilisation with amphotericin B. This Na⁺ current was increased (control 7.5 ± 2.7, 3 mM 1-EBIO 15.5 ±4.7, 0.3 mM DC-EBIO 25.7 ± 7.5 and 0.3 mM RLZ 21.2 ± 5.9, p<0.05). In conclusion, 1-EBIO and DC-EBIO, but not RLZ increased lung epithelial vectorial Na⁺ transport via an I_K dependent mechanism. Furthermore, the apical amiloride sensitive Na⁺ conductance was increased by all substances, suggesting an additional unknown stimulatory effect on apical Na⁺ permeability. Supported by: DFG Th626 (to UT) and Medizinische Fakultät, Ulm P770 (to OW)