In:
American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 292, No. 6 ( 2007-06), p. G1683-G1694
Abstract:
Pathological rates of gallbladder salt and water transport may promote the formation of cholesterol gallstones. Because prairie dogs are widely used as a model of this event, we characterized gallbladder ion transport in animals fed control chow by using electrophysiology, ion substitution, pharmacology, isotopic fluxes, impedance analysis, and molecular biology. In contrast to the electroneutral properties of rabbit and Necturus gallbladders, prairie dog gallbladders generated significant short-circuit current ( I sc ; 171 ± 21 μA/cm 2 ) and lumen-negative potential difference (−10.1 ± 1.2 mV) under basal conditions. Unidirectional radioisotopic fluxes demonstrated electroneutral NaCl absorption, whereas the residual net ion flux corresponded to I sc . In response to 2 μM forskolin, I sc exceeded 270 μA/cm 2 , and impedance estimates of the apical membrane resistance decreased from 200 Ω·cm 2 to 13 Ω·cm 2 . The forskolin-induced I sc was dependent on extracellular HCO 3 − and was blocked by serosal 4,4′-dinitrostilben-2,2′-disulfonic acid (DNDS) and acetazolamide, whereas serosal bumetanide and Cl − ion substitution had little effect. Serosal trans-6-cyano-4-( N-ethylsulfonyl- N-methylamino)-3-hydroxy-2,2-dimethyl-chroman and Ba 2+ reduced I sc , consistent with the inhibition of cAMP-dependent K + channels. Immunoprecipitation and confocal microscopy localized cystic fibrosis transmembrane conductance regulator protein (CFTR) to the apical membrane and subapical vesicles. Consistent with serosal DNDS sensitivity, pancreatic sodium-bicarbonate cotransporter protein pNBC1 expression was localized to the basolateral membrane. We conclude that prairie dog gallbladders secrete bicarbonate through cAMP-dependent apical CFTR anion channels. Basolateral HCO 3 − entry is mediated by DNDS-sensitive pNBC1, and the driving force for apical anion secretion is provided by K + channel activation.
Type of Medium:
Online Resource
ISSN:
0193-1857
,
1522-1547
DOI:
10.1152/ajpgi.00268.2006
Language:
English
Publisher:
American Physiological Society
Publication Date:
2007
detail.hit.zdb_id:
1477329-6
SSG:
12
Bookmarklink
