Intracellular calcium modulates gallbladder ion transport

Abstract

Although experimentally induced cholesterol gallstone formation has been associated with altered gallbladder (GB) absorption and increased biliary Ca 2+, the relationship between these events remains unclear. Recent studies suggest that extracellular Ca 2+ ([Ca 2+] ec) influences GB ion transport. Whether the effects of [Ca 2+] ec are mediated by changes in intracellular Ca 2+ ([Ca 2+] ic) has not been determined. This study was designed to define the effects of altered [Ca 2+] ic on GB ion transport. Prairie dog GBs were mounted in a Ussing chamber and short-circuit current ( I sc), potential difference ( V ms), and resistance ( R t) were recorded. Mucosal surfaces were exposed to either Dantrolene (Dt) or nickel (Ni 2+). Dt “traps” [Ca 2+] ic within intracellular organelles, thereby lowering cytosolic Ca 2+; and Ni 2+ prevents influx of [Ca 2+] ec, presumably by binding Ca 2+ channels. Although Dt reduced both I sc and V ms ( P < 0.01), these effects were transient. Transport recovery was probably due to increased [Ca 2+] ec influx with restoration of [Ca 2+] ic. Ni 2+ resulted in sustained decreases in I sc and V ms ( P < 0.05) despite subsequent addition of 10 m M Ca 2+. These findings are consistent with the prevention of [Ca 2+] ec influx by Ni 2+. We conclude that: (1) [Ca 2+] ic may be a modulator of GB ion transport and (2) previously reported [Ca 2+] ec effects on ion transport may be mediated through [Ca 2+] ic concentration changes.