Bile acids induce a cationic current, depolarizing pancreatic acinar cells and increasing the intracellular Na+ concentration.
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 Ca(2+)-dependent and Ca(2+)-independent components of the Na(+) concentration increase. The Ca(2+)-independent component was resolved in conditions when the cytosolic Ca(2+) 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 Ca(2+)-dependent component of intracellular Na(+) increase was clearly seen during stimulation with the calcium-releasing agonist acetylcholine. During acetylcholine-induced Ca(2+) oscillations the recovery of cytosolic Na(+) was much slower than the recovery of Ca(2+), creating a possibility for the summation of Na(+) transients. The bile-induced Ca(2+)-independent current was found to be carried primarily by Na(+) and K(+), with only small Ca(2+) and Cl(-) contributions. Measurable activation of such a cationic current could be produced by a very low concentration of taurolithocholic acid 3-sulfate (10 microm). 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.
Voronina
Svetlana G
SG
Physiological Laboratory, University of Liverpool, Liverpool L69 3BX, United Kingdom.
Gryshchenko
Olexyi V
OV
Gerasimenko
Oleg V
OV
Green
Anne K
AK
Petersen
Ole H
OH
Tepikin
Alexei V
AV
D000818:Animals; D001647:Bile Acids and Salts / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000737:chemistry; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D051379:Mice; D010179:Pancreas / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012964:Sodium / Q000378:metabolism / Q000502:physiology*
D001647:Bile Acids and Salts; D002614:Chelating Agents; D005456:Fluorescent Dyes; D004533:Egtazic Acid; D012964:Sodium; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium