Despite the identification of cholangiocytes in the liver and unipolar brush cells in the cerebellum as sites of expression, the physiological function of the bile acid-sensitive ion channel (BASIC) remains unknown. Rat BASIC (rBASIC) and mouse BASIC (mBASIC) share 97% of their amino acid sequence but show strikingly different biophysical properties. rBASIC is inactive at rest while mBASIC is constitutively active, when expressed in Xenopus oocytes. This conundrum rendered the identification of the physiological function even more difficult. In this study, we investigated the electrophysiological and pharmacological properties of BASIC from rat, mouse, and human in Hek293 cells using the patch clamp technique. Surprisingly, in Hek293 cells, rBASIC and mBASIC showed almost completely identical properties. Both are blocked by extracellular Ca2+ and thus are inactive at rest; both are selective for Na+, show similar affinities for extracellular Ca2+, were inhibited by diminazene, and activated by various bile acids. This is in contrast to previous results derived from Xenopus oocytes as expression system and suggests that the cell type is important for shaping the biophysical properties of BASIC. Furthermore, we compared hBASIC with rBASIC and mBASIC and observed similar properties between these channels with one exception: the bile acid sensitivity profile of hBASIC is different from rBASIC and mBASIC; hBASIC is more sensitive to bile acids which are abundant in human bile but not in rodent bile. Taken together, these results suggest similar physiological roles for BASIC in different species.
Keywords: ASIC; BASIC; Bile acid; Cation channel; ENaC.