Journal
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volume 288, Issue 3, Pages G457-G465Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00381.2004
Keywords
sodium-calcium exchange
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Funding
- NIDDK NIH HHS [DK-33491-18] Funding Source: Medline
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Stimulation of muscarinic receptors in duodenal mucosa raises intracellular Ca2+, which regulates ion transport, including HCO3- secretion. However, the underlying Ca2+ handling mechanisms are poorly understood. The aim of the present study was to determine whether Na+/Ca2+ exchanger (NCX) plays a role in the regulation of duodenal mucosal ion transport and HCO3- secretion by controlling Ca2+ homeostasis. Mouse duodenal mucosa was mounted in Ussing chambers. Net ion transport was assessed as short-circuit current (I-sc), and HCO3- secretion was determined by pH-stat. Expression of NCX in duodenal mucosae was analyzed by Western blot, and cytosolic Ca2+ in duodenocytes was measured by fura 2. Carbachol (100 muM) increased I-sc in a biphasic manner: an initial transient peak within 2 min and a later sustained plateau starting at 10 min. Carbachol-induced HCO3- secretion peaked at 10 min. 2-Aminoethoxydiphenylborate (2-APB, 100 muM) or LiCl (30 mM) significantly reduced the initial peak in I-sc by 51 or 47%, respectively, and abolished the plateau phase of I-sc without affecting HCO3- secretion induced by carbachol. Ryanodine (100 muM), caffeine (10 mM), and nifedipine (10 muM) had no effect on either response to carbachol. In contrast, nickel (5 mM) and KB-R7943 (10-30 muM) significantly inhibited carbachol-induced increases in duodenal mucosal I-sc and HCO3- secretion. Western blot analysis showed expression of NCX1 proteins in duodenal mucosae, and functional NCX in duodenocytes was demonstrated in Ca2+ imaging experiments where Na+ depletion elicited Ca2+ entry via the reversed mode of NCX. These results indicate that NCX contributes to the regulation of Ca2+-dependent duodenal mucosal ion transport and HCO3- secretion that results from stimulation of muscarinic receptors.
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