Acid-sensing ion channels (ASICs) are non-voltage-gated sodium channels transiently activated by extracellular protons and belong to the epithelial sodium channel (ENaC)/Degenerin family of ion channels. Bile acids have been shown to activate two members of this family, the bile acid sensitive ion channel (BASIC) (1, 2) and ENaC (3). The aim of the present study was to investigate whether bile acids also can modulate ASIC function. For this purpose human ASIC1a was heterologously expressed in Xenopus laevis oocytes. Whole-cell currents and single-channel currents were measured using the two-electrode voltage clamp technique and outside-out patch-clamp recordings, respectively. Values are presented as mean ± S.E.M. Paired Student’s t-test was used for statistical analysis. Exposing oocytes to tauro-conjugated cholic (t-CA), deoxycholic (t-DCA) and chenodeoxycholic (t-CDCA) acid (500 µM) at pH 7.4 did not activate ASIC1a-mediated whole-cell currents. This is in agreement with a report that rat BASIC but not rat ASIC1a could be activated by tauroursodeoxycholic acid (4). We hypothesized that bile acids may not activate ASIC per se but may modify channel activation by protons. Indeed, we observed that ASIC1a whole-cell currents elicited by pH 5.5 were significantly increased in the presence of bile acids. In the presence of t-CA the peak inward current elicited by pH 5.5 was increased by a factor of 1.41±0.06, whereas t-DCA and t-CDCA increased the proton-activated currents by a factor of 2.07±0.15 and 2.09±0.09, respectively (p<0.001, n=18). Application of t-DCA was accompanied by a significant ~15% reduction of the single-channel current amplitude of ASIC1a (p<0.001, n=13). This suggests an interaction of t-DCA with a region close to the channel pore. Analysis of the chicken ASIC1 crystal structure (5) revealed the presence of co-crystallized n-dodecyl-β-D-maltoside detergent molecules in the pore region of the channel. Bile acids are amphiphilic substances and can behave as detergents. Therefore, we speculated that bile acids and maltoside detergent bind to ASIC1a at similar sites and may affect channel activity in a similar way. Indeed, application of maltoside detergent (10 µM) mimicked the effect of bile acids and led to a significant increase of proton-activated ASIC1a currents by a factor of about 1.4 (p<0.001, n=19). Finally, molecular docking analysis predicted binding of bile acids to the pore region in the open conformation of the channel. We conclude that bile acids potentiate proton-activated ASIC1a currents probably by stabilizing the open state of the channel.