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Bile acids induce a cationic current, depolarizing pancreatic acinar cells and increasing the intracellular Na+ concentration

Voronina, Svetlana G., Gryshchenko, Olexyi V., Gerasimenko, Oleg Vsevolodovich, Green, Anne K., Petersen, Ole Holger and Tepikini, Alexei V. 2005. Bile acids induce a cationic current, depolarizing pancreatic acinar cells and increasing the intracellular Na+ concentration. Journal of Biological Chemistry 280 (3) , pp. 1764-1770. 10.1074/jbc.M410230200

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Abstract

Biliary disease is a major cause of acute pancreatitis. In this study we investigated the electrophysiological effects of bile acids on pancreatic acinar cells. In perforated patch clamp experiments we found that taurolithocholic acid 3-sulfate depolarized pancreatic acinar cells. At low bile acid concentrations this occurred without rise in the cytosolic calcium concentration. Measurements of the intracellular Na+ concentration with the fluorescent probe Sodium Green revealed a substantial increase upon application of the bile acid. We found that bile acids induce Ca2+-dependent and Ca2+-independent components of the Na+ concentration increase. The Ca2+-independent component was resolved in conditions when the cytosolic Ca2+ level was buffered with a high concentration of the calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA). The Ca2+-dependent component of intracellular Na+ increase was clearly seen during stimulation with the calcium-releasing agonist acetylcholine. During acetylcholine-induced Ca2+ oscillations the recovery of cytosolic Na+ was much slower than the recovery of Ca2+, creating a possibility for the summation of Na+ transients. The bile-induced Ca2+-independent current was found to be carried primarily by Na+ and K+, with only small Ca2+ and Cl– contributions. Measurable activation of such a cationic current could be produced by a very low concentration of taurolithocholic acid 3-sulfate (10 μm). This bile acid induced a cationic current even when applied in sodium- and bicarbonate-free solution. Other bile acids, taurochenodeoxycholic acid, taurocholic acid, and bile itself also induced cationic currents. Bile-induced depolarization of acinar cells should have a profound effect on acinar fluid secretion and, consequently, on transport of secreted zymogens.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Systems Immunity Research Institute (SIURI)
Publisher: American Society for Biochemistry and Molecular Biology
ISSN: 0021-9258
Last Modified: 04 Jun 2017 06:38
URI: http://orca.cf.ac.uk/id/eprint/63133

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