The hypertonic solution was applied over the entire island on which the autaptic neuron was located. This solution evoked a large initial transient current that declined to a low steady-state level over about 3 sec; hypertonic solution was applied for 4–5 sec in order to deplete the readily releasable pool fully. The size of the readily releasable pool was calculated by integrating the current evoked by the hypertonic solution to yield a charge value. To estimate the readily releasable pool size more accurately, we corrected the integral of the current by subtracting away the amount of steadystate exocytosis that occurred during the hypertonic solution flow. Treatment of hepatitis C is based on a combination of pegylated interferon-a and ribavirin. First viral protease inhibitors have been licensed in 2011 and substantially improve therapy response. However, since drug resistant variants are rapidly selected during monotherapy, these drugs complement but do not replace the previous IFN-based regimen. HCV patients that have high serum levels of BAs respond poorly to IFN therapy and are more prone to develop hepatic fibrosis. Bas therefore were suggested to play an important role in pathogenesis and therapy response of HCV. BAs are synthesized in hepatocytes using cholesterol as precursor and are then secreted from the liver via the bile duct. To increase solubility, these molecules are conjugated with glycine or taurin prior to Magnoflorine-iodide secretion. The primary BAs in humans are cholic acid and chenodeoxycholic acid. Intestinal bacteria dehydroxylate primary BAs thus converting them to secondary BAs, such as deoxycholic acid and lithocholic acid. A tertiary BA, ursodeoxycholic acid, is of minor importance, because it only represents 3% of the total bile acid pool in humans. Besides their well-established functions in resorption of lipid-soluble nutrients and cholesterol catabolism, BAs also play an important role as signaling molecules. For instance, the nuclear farnesoid Xreceptor is activated by physiological concentrations of bile salts. As a nuclear receptor, it regulates multiple genes which are involved in lipid, glucose and bile acid metabolism. Notably, the activation of FXR also leads to an upregulation of apolipoprotein CII, which activates the lipoprotein lipase, an enzyme that has been implicated to promote Magnoflorine entry and reduce infectivity of cell-culture derived hepatitis C virus particles. Moreover, BAs repress secretion of apolipoprotein B containing lipoproteins through inhibition of the microsomal triglyceride transfer protein. As a consequence, they may influence secretion of infectious HCV particles which depends on MTP and apoB secretion. Collectively, these data suggest that endocrine functions of BAs regulate host cell pathways which may influence RNA-replication, virus production and infectivity of HCV particles and in turn treatment efficacy and viral pathogenesis. The influence of BAs on HCV GT1 and GT2a subgenomic replicons has been reported previously. These data suggested that selectively GT1 was stimulated by BAs while GT2a was refractory to regulation by BAs. Moreover, it was unclear which step of the viral life cycle were influenced. Therefore, we investigated the effect of BAs on different stages of the HCV replication cycle and analyzed GT-dependent viral factors essential for regulation by BAs. With the exception of JFH1, most HCV consensus genomes replicate poorly in cell culture requiring specific replication enhancing mutations to increase replication to levels sufficient for experimental analyses. Notably, at least in case of Con1, many of these REMs interfere with production of infectious progeny particles and highly cell culture adapted Con1 genomes are attenuated in vivo.