IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2010;2(2):125-136

Original Article
Molecular and functional characterization of non voltage-operated Ca2+ entry in
gastrointestinal neuroendocrine tumor cells

Sasi Arunachalam, Tetyana Zhelay, David R. Giovannucci

Department of Neurosciences, University of Toledo College of Medicine, Toledo OH 43614, USA.

Received April 27, 2010, accepted May 15, 2010, available online May 19, 2010

Abstract: Ca2+ entry through non-voltage operated channels serves as a key signaling component for tumor progression
in a variety of cancers including prostate, colon and breast. As a starting point for an inquiry into the role of Ca2+
signaling pathways in gastroenteropancreatic neuroendocrine cancers, including carcinoid, we characterized Ca2+
entry in a set of human carcinoid cell lines originating in the foregut, midgut and hindgut. In the current study, we
provide molecular and functional evidence for store-operated and other non-voltage operated Ca2+ permeable channels
in carcinoid tumor cell lines. RT-PCR technique was used to profile an array of non voltage-operated Ca2+ channels
in carcinoid cell lines. Live-cell imaging methods were used to functionally assess store operated Ca2+ entry
(SOCE) following depletion of ER Ca2+ stores by cyclopiazonic acid. Treatment with pharmacological inhibitors of
SOCE generally reduced Ca2+ entry. We also demonstrated that SOCE in some carcinoid cell lines was activated by
neurotransmitter suggesting that Ca2+ entry through specific channels may be important for mediating neural,
paracrine or autocrine signals in the gut in health and disease such as carcinoid cancer. (IJPPP1004003).

Key words: Store-operated, Orai, STIM, TRP, fura-2, carcinoid

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Address all correspondence to:
David Giovannucci, PhD
Department of Neurosciences
College of Medicine/University of Toledo Health Science Campus
Toledo, OH 43614, USA.
Tel: 419-383-5004