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

J. Biol. Chem., Vol. 279, Issue 12, 11106-11111, March 19, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/12/11106    most recent M400005200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gore, A. Articles by Sekler, I. Search for Related Content PubMed PubMed Citation Articles by Gore, A. Articles by Sekler, I. Social Bookmarking                      What's this?

Inhibitory Mechanism of Store-operated Ca²⁺ Channels by Zinc^*

Ariel Gore, Arie Moran, Michal Hershfinkel¶, and Israel Sekler||

From the Physiology and ^¶Morphology, Faculty of Health Science and the Zlotowski Center for Neuroscience, Ben Gurion University of the Negev, POB 653, Beer-Sheva, 84105, Israel

Capacitative calcium influx plays an important role in shaping the Ca²⁺ response of various tissues and cell types. Inhibition by heavy metals is a hallmark of store-operated calcium channel (SOCC) activity. Paradoxically, although zinc is the only potentially physiological relevant ion, it is the least investigated in terms of inhibitory mechanism. In the present study, we characterize the inhibitory mechanism of the SOCC by Zn²⁺ in the human salivary cell line, HSY, and rat salivary submandibular ducts and acini by monitoring SOCC activity using fluorescence imaging. Analysis of Zn²⁺ inhibition indicated that Zn²⁺ acts as a competitive inhibitor of Ca²⁺ influx but does not permeate through the SOCC, suggesting that Zn²⁺ interacts with an extracellular site of SOCC. Application of the reducing agents, dithiothreitol (DTT) and -mercaptoethanol, totally eliminated Zn²⁺ and Cd²⁺ inhibition of SOCC, suggesting that cysteines are part of the Zn²⁺ and Cd²⁺ binding site. Interestingly, reducing conditions failed to eliminate the inhibition of SOCC by La³⁺ and Gd³⁺, indicating that the Zn²⁺ and lanthanides binding sites are distinct. Finally, we show that changes in redox potential and Zn²⁺ are regulating, via SOCC activity, the agonist-induced Ca²⁺ response in salivary ducts. The presence of a specific Zn²⁺ site, responsive to physiological Zn²⁺ and redox potential, may not only be instrumental for future structural studies of various SOCC candidates but may also reveal novel physiological aspects of the interaction between zinc, redox potential, and cellular Ca²⁺ homeostasis.

Received for publication, January 2, 2004

^* This work was supported by German-Israeli Foundation for Scientific Research and Development Grant 10588099.01/98, Israeli Science Foundation (ISF) Grant 456/02.1 (to I. S. and A. M.), and ISF equipment Grant 456/02.2 (to I. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom corresponding may be addressed. Tel.: 972-8-6477331; Fax: 972-8-6477628; E-mail: arie{at}bgumail.bgu.ac.il. || To whom corresponding may be addressed. Tel.: 972-8-6477328; Fax: 972-8-6477628; E-mail: sekler{at}bgumail.bgu.ac.il.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B. A. Kachoei, R. J. Knox, D. Uthuza, S. Levy, L. K. Kaczmarek, and N. S. Magoski A Store-Operated Ca2+ Influx Pathway in the Bag Cell Neurons of Aplysia J Neurophysiol, November 1, 2006; 96(5): 2688 - 2698. [Abstract] [Full Text] [PDF]