HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/C979    most recent 00577.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Naik, H. B. Articles by Soybel, D. I. PubMed PubMed Citation Articles by Naik, H. B. Articles by Soybel, D. I.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Secretory state regulates Zn²⁺ transport in gastric parietal cell of the rabbit

Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Submitted 10 November 2008 ; accepted in final form 4 August 2009

Secretory compartments of neurons, endocrine cells, and exocrine glands are acidic and contain high levels of labile Zn²⁺. Previously, we reported evidence that acidity is regulated, in part, by the content of Zn²⁺ in the secretory [i.e., tubulovesicle (TV)] compartment of the acid-secreting gastric parietal cell. Here we report studies focusing on the mechanisms of Zn²⁺ transport by the TV compartment in the mammalian (rabbit) gastric parietal cell. Uptake of Zn²⁺ by isolated TV structures was monitored with a novel application of the fluorescent Zn²⁺ reporter N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ). Uptake was suppressed by removal of external ATP or blockade of H⁺-K⁺-ATPase that mediates luminal acid secretion. Uptake was diminished with dissipation of the proton gradient across the TV membrane, suggesting Zn²⁺/H⁺ antiport as the connection between Zn²⁺ uptake and acidity in the TV lumen. In isolated gastric glands loaded with the reporter fluozin-3, inhibition of H⁺-K⁺-ATPase arrested the flow of Zn²⁺ from the cytoplasm to the TV compartment and secretory stimulation with forskolin enhanced vectorial movement of cytoplasmic Zn²⁺ into the tubulovesicle/lumen (TV/L) compartment. Our findings suggest that Zn²⁺ accumulation in the TV/L compartment is physiologically coupled to secretion of acid. These findings offer novel insight into mechanisms regulating Zn²⁺ homeostasis in the gastric parietal cell and potentially other cells in which acidic subcellular compartments serve signature functional roles.

gastric gland; tubulovesicles; zinc; acidity regulation