The bile acid-sensitive ion channel (BASIC) mediates bile acid-dependent currents in bile duct epithelial cells

Abstract

The bile acid-sensitive ion channel (BASIC) is a member of the Deg/ENaC family of ion channels that is activated by bile acids. Despite the identification of cholangiocytes in the liver and unipolar brush cells in the cerebellum as sites of expression, the physiological function of BASIC in these cell types is not yet understood. Here we used a cholangiocyte cell line, normal rat cholangiocytes (NRCs), which expresses BASIC to study the role of the channel in epithelial transport using Ussing chamber experiments. Apical application of bile acids induced robust and transient increases in transepithelial currents that were carried by Na+ and partly blocked by the BASIC inhibitor diminazene. Genetic ablation of the BASIC gene in NRC using a CRISPR-cas9 approach resulted in a decrease of the bile acid-mediated response that matched the diminazene-sensitive current in NRC WT cells, suggesting that cholangiocytes respond to bile acids with a BASIC-mediated Na+ influx. Taken together, we have identified BASIC as a component of the cholangiocyte transport machinery, which might mediate a bile acid-dependent modification of the bile and thus control bile flux and composition.

Functional analysis in a model sea anemone reveals phylogenetic complexity and a role in cnidocyte discharge of DEG/ENaC ion channels

“…BASIC is gated by bile acids and blocked by extracellular Ca 2+ ions 9 . It is found in the epithelial cells of the bile ducts, but its physiological function remains uncertain 10 . While ENaC evolved early in vertebrates and might have aided in the osmoregulatory adaption during the transition of vertebrates to land 11 , proton-sensitive ASICs are also present in non-vertebrate deuterostomes and some protostomes and likely evolved before the Cambrian explosion 12 , 13 .…”

Functional analysis in a model sea anemone reveals phylogenetic complexity and a role in cnidocyte discharge of DEG/ENaC ion channels

“…BASIC is gated by bile acids and blocked by extracellular Ca 2+ ions (10). It is found in the epithelial cells of the bile ducts, but its physiological function remains uncertain (11).…”

“…BASIC is gated by bile acids and blocked by extracellular Ca 2+ ions ( 10 ). It is found in the epithelial cells of the bile ducts, but its physiological function remains uncertain ( 11 ). While ENaC evolved early in vertebrates and might have aided in the osmoregulatory adaption during the transition of vertebrates to land ( 12 ), proton-sensitive ASICs are also present in non-vertebrate deuterostomes and some protostomes and likely evolved before the Cambrian explosion ( 13, 14 ).…”

Secondary bile acids and the biliary epithelia: The good and the bad

“…HDCA is reported as the strongest regulator of BA-sensitive ion channel (BASIC) that is normally expressed in brain, intestine and cholangiocytes only, within the liver[ 65 ]. While the exact physiologic function of cholangiocyte BASIC has not been well established, evidences demonstrate enhanced activity of this channel, with increased trans-epithelial ion transport, after exposure to HDCA[ 66 ]. This suggests BASIC as a further possible regulator of biliary secretion.…”