Cholestatic bile acids inhibit gap junction permeability in rat hepatocyte couplets and normal rat cholangiocytes.

Background/aims: The aim of this work was to study the effects of different bile acids on the permeability of gap junction channels (PGJC). We also looked at the effects of some bile acids on the coordination of intercellular calcium oscillations.

Methods: The permeability of gap junctions was assessed by fluorescent dye transfer and calcium signalling on fluorescent microscopy.

Results: Cholestatic bile acids such as taurolithocholate, taurolithocholate-sulfate and taurochenodeoxycholate inhibit the permeability of gap junctions in a dose-dependent and reversible manner in hepatocytes. Experiments performed in other cell types suggest that this effect is specific for cells having bile salt transporters, independently of the type of connexin expressed in these cells. Thus, cholestatic bile acids inhibit PGJC in normal rat cholangiocytes which express Cx43, but not in HeLa cells transfected with Cx26 or 32, which are expressed in hepatocytes. Calcium oscillations induced by bile acids in rat hepatocyte couplets are not coordinated and, by inhibiting the PGJC, cholestatic bile acids prevent the coordination of calcium oscillations induced by noradrenaline in these cells.

Conclusions: Cholestatic, but not choleretic bile acids inhibit the PGJC in cells able to accumulate bile acids. This inhibition might contribute to the cholestatic effect of these bile acids.