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Updated: Jun 3, 2026
In Situ Ca2+ Imaging of the Enteric Nervous System
Published on: January 29, 2015
Molecular and functional characterization of non voltage-operated Ca entry in gastrointestinal neuroendocrine tumor
Sasi Arunachalam1, Tetyana Zhelay, David R Giovannucci
1Department of Neurosciences, University of Toledo College of Medicine Toledo OH 43614, USA.
Abstract:
Ca(2+) 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 Ca(2+) signaling pathways in gastroenteropancreatic neuroendocrine cancers, including carcinoid, we characterized Ca(2+) 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 Ca(2+) permeable channels in carcinoid tumor cell lines. RT-PCR technique was used to profile an array of non voltage-operated Ca(2+) channels in carcinoid cell lines. Live-cell imaging methods were used to functionally assess store operated Ca(2+) entry (SOCE) following depletion of ER Ca(2+) stores by cyclopiazonic acid. Treatment with pharmacological inhibitors of SOCE generally reduced Ca(2+) entry. We also demonstrated that SOCE in some carcinoid cell lines was activated by neurotransmitter suggesting that Ca(2+) 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.
Insights
Calcium (Ca2+) entry via non-voltage operated channels is crucial for carcinoid cancer progression. This study identifies store-operated calcium entry (SOCE) in carcinoid cells, suggesting a role in tumor signaling.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Non-voltage operated calcium channels (Ca2+) are implicated in tumor progression across various cancers.
- Gastroenteropancreatic neuroendocrine tumors (carcinoids) are a significant group of cancers where Ca2+ signaling roles are underexplored.
Purpose of the Study:
- To investigate the role and mechanisms of Ca2+ entry in human carcinoid cell lines.
- To characterize the presence and function of store-operated calcium entry (SOCE) and other non-voltage operated Ca2+ channels in carcinoid tumors.
Main Methods:
- Reverse transcription polymerase chain reaction (RT-PCR) was employed to profile Ca2+ channel expression.
- Live-cell imaging was used to assess functional store-operated Ca2+ entry (SOCE) after endoplasmic reticulum (ER) Ca2+ store depletion.
- Pharmacological inhibitors were used to evaluate the impact on Ca2+ influx.
Main Results:
- Molecular evidence for various non-voltage operated Ca2+ channels was found in carcinoid cell lines.
- Functional SOCE was confirmed in carcinoid cells, with its activity generally reduced by SOCE inhibitors.
- Neurotransmitter activation of SOCE was observed in some cell lines, indicating potential roles in signaling.
Conclusions:
- Carcinoid tumor cells possess functional store-operated calcium entry (SOCE) and other non-voltage operated Ca2+ channels.
- Ca2+ entry pathways, including SOCE, may play a critical role in mediating neural, paracrine, or autocrine signaling in carcinoid cancers.
- These findings highlight Ca2+ signaling as a potential therapeutic target in carcinoid oncology.
