title: Apical and basolateral Ca(2) channels modulate cytosolic Ca(2)+ in gallbladder epithelia.
abstract: Gallstone formation is associated with altered gallbladder (GB) ion transport and increased concentration of GB bile Ca2+. Recent studies show that increased cytosolic Ca2+ ([Ca2+]i) stimulates GB Cl- secretion. However, the mechanism by which extracellular Ca2+ ([Ca2+]e) enters the cytosol remains unclear. We tested the hypothesis that entry of [Ca2+] into cytosol occurs via apical and basolateral membrane Ca2+ channels. Prairie dog GBs were mounted in Ussing chambers, standard electrophysiologic parameters were recorded, and unidirectional Cl- fluxes (J, microEq x cm(-2) x hr(-1) were measured using 36Cl at various mucosal Ca2+ in the absence or presence of mucosal lanthanum (La3+), a non-diffusible Ca2+ channel blocker. Serosal [Ca2+]e was maintained at trace levels. In the absence of mucosal La3+, short circuit current (Isc) showed a positive correlation with mucosal [Ca2+]e as represented by a second order polynomial equation (y = 4.1 + 2.5x - 0.73x(2), r = 0.68, P < 0.001). In contrast, unidirectional mucosa to serosa Cl flux (JCl/ms) was inversely correlated with [Ca2+] (y = 47.9 - 8.7x + 0.9x(2), r = 0.51, P <.05) Addition of 1 mM mucosal La3+ blunted the effects of [Ca2+]e on electrophysiologic parameters and JCl/ms. However, basolateral repletion with 5 mM Ca2+ reverses the blocking effects of La3+ on JCl/ms. These data suggest that [Ca2+]e enters the cytosol via apical and basolateral Ca2+ channels. We conclude that GB apical Ca2+ channels may represent a pathway for biliary Ca2+ entry into the cell and therefore may represent an important regulatory pathway for GB ion transport during gallstone formation.
authors.affiliation: Department of Surgery, Medical College of Pennsylvania and Hahnemann University, Philadelphia 19129, USA.
authors.forename: D I
authors.initials: DI
authors.lastname: Giurgiu
authors.forename: J A
authors.initials: JA
authors.lastname: Karam
authors.forename: A K
authors.initials: AK
authors.lastname: Madan
authors.forename: J J
authors.initials: JJ
authors.lastname: Roslyn
authors.forename: M Z
authors.initials: MZ
authors.lastname: Abedin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005704:Gallbladder / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D009092:Mucous Membrane / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D012044:Regression Analysis; D012589:Sciuridae
chemical_list: D015220:Calcium Channels; D007811:Lanthanum; D002118:Calcium