title: Intracellular calcium modulates gallbladder ion transport.
abstract: Although experimentally induced cholesterol gallstone formation has been associated with altered gallbladder (GB) absorption and increased biliary Ca2+, the relationship between these events remains unclear. Recent studies suggest that extracellular Ca2+ ([Ca2+]ec) influences GB ion transport. Whether the effects of [Ca2+]ec are mediated by changes in intracellular Ca2+ ([Ca2+]ic) has not been determined. This study was designed to define the effects of altered [Ca2+]ic on GB ion transport. Prairie dog GBs were mounted in a Ussing chamber and short-circuit current (Isc), potential difference (Vms), and resistance (Rt) were recorded. Mucosal surfaces were exposed to either Dantrolene (Dt) or nickel (Ni2+). Dt "traps" [Ca2+]ic within intracellular organelles, thereby lowering cytosolic Ca2+; and Ni2+ prevents influx of [Ca2+]ec, presumably by binding Ca2+ channels. Although Dt reduced both Isc and Vms (P less than 0.01), these effects were transient. Transport recovery was probably due to increased [Ca2+]ec influx with restoration of [Ca2+]ic. Ni2+ resulted in sustained decreases in Isc and Vms (P less than 0.05) despite subsequent addition of 10 mM Ca2+. These findings are consistent with the prevention of [Ca2+]ec influx by Ni2+. We conclude that: (1) [Ca2+]ic may be a modulator of GB ion transport and (2) previously reported [Ca2+]ec effects on ion transport may be mediated through [Ca2+]ic concentration changes.
authors.affiliation: Research Service, Sepulveda VAMC, California.
authors.forename: J A
authors.initials: JA
authors.lastname: Cates
authors.forename: K D
authors.initials: KD
authors.lastname: Saunders
authors.forename: M Z
authors.initials: MZ
authors.lastname: Abedin
authors.forename: J J
authors.initials: JJ
authors.lastname: Roslyn
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology; D005704:Gallbladder / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism*; D007477:Ions; D008297:Male; D009532:Nickel / Q000494:pharmacology; D004369:Pentetic Acid / Q000494:pharmacology; D012589:Sciuridae
chemical_list: D007477:Ions; D004369:Pentetic Acid; D009532:Nickel; D003620:Dantrolene; D002118:Calcium