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Electrogenic bicarbonate secretion by prairie dog gallbladder.

A James Moser¹, A Gangopadhyay, N A Bradbury

¹Univ. of Pittsburgh School of Medicine, 497 Scaife Hall; 3550 Terrace St.; Pittsburgh, PA 15261, USA. moseraj@upmc.edu

American Journal of Physiology. Gastrointestinal and Liver Physiology

|March 17, 2007

Summary

Prairie dog gallbladder actively secretes bicarbonate via CFTR anion channels, a process crucial for understanding cholesterol gallstone formation. This active transport mechanism differs from other species and involves specific ion channel regulation.

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Area of Science:

Physiology
Gastroenterology
Molecular Biology

Background:

Pathological gallbladder salt and water transport is implicated in cholesterol gallstone formation.
Prairie dogs serve as a relevant animal model for studying gallstone pathogenesis.

Purpose of the Study:

To characterize the electrophysiological and molecular mechanisms of gallbladder ion transport in prairie dogs.
To elucidate the role of specific ion channels and transporters in prairie dog gallbladder function.

Main Methods:

Electrophysiology (short-circuit current, potential difference)
Ion substitution and pharmacological inhibition
Isotopic flux measurements
Impedance analysis
Molecular biology techniques (immunoprecipitation, confocal microscopy)

Main Results:

Prairie dog gallbladder exhibits significant basal short-circuit current and lumen-negative potential difference, unlike rabbit and Necturus.
Forskolin stimulation increased short-circuit current and decreased apical membrane resistance, indicating active ion secretion.
Secretion is dependent on extracellular bicarbonate and involves cystic fibrosis transmembrane conductance regulator (CFTR) anion channels and pancreatic sodium-bicarbonate cotransporter 1 (pNBC1).

Conclusions:

Prairie dog gallbladder actively secretes bicarbonate through cAMP-dependent apical CFTR anion channels.
Basolateral bicarbonate entry is mediated by DNDS-sensitive pNBC1.
K+ channel activation provides the driving force for apical anion secretion, highlighting a unique transport mechanism in this gallstone model.