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Epithelial Ca2+ entry channels: transcellular Ca2+ transport and beyond
Ji-Bin Peng1, Edward M Brown, Matthias A Hediger
1Membrane Biology Program and Renal and Endocrine-Hypertension Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
The Journal of Physiology
|July 19, 2003
Summary
The TRPV family includes calcium channels CaT1 (TRPV6) and ECaC (TRPV5), crucial for calcium absorption in tissues like the intestine and kidney. CaT1
Area of Science:
- Molecular Biology
- Cell Physiology
- Ion Channel Function
Background:
- The Transient Receptor Potential Vanilloid (TRPV) family comprises six members, with TRPV6 (CaT1) and TRPV5 (ECaC) being highly calcium-selective channels.
- Unlike other TRPV channels that act as sensors, CaT1 and ECaC function as apical calcium entry mechanisms in absorptive and secretory epithelia.
Purpose of the Study:
- To elucidate the distinct roles and regulation of CaT1 and ECaC in calcium transport.
- To explore the broader functions of CaT1 beyond calcium absorption, including its role in exocrine tissues and cancer.
Main Methods:
- Expression analysis of CaT1 and ECaC in various tissues.
- Functional characterization of calcium channel activity and regulation.
- Investigation of CaT1 involvement in cellular calcium signaling pathways.
Main Results:
- CaT1 is predominantly found in the intestine and placenta, while ECaC is concentrated in the kidney tubules.
- CaT1 is regulated by 1,25-dihydroxyvitamin D3 and exhibits calcium-dependent feedback inhibition.
- ECaC displays slow inactivation kinetics and is primarily regulated by renal calcium load.
- CaT1 is also expressed in exocrine tissues and contributes to store-operated calcium entry in lymphocytes and cancer cells.
- Upregulated CaT1 expression is observed in prostate and other epithelial cancers.
Conclusions:
- CaT1 and ECaC are specialized calcium channels with distinct tissue distribution and regulatory mechanisms.
- CaT1 plays a significant role in intestinal calcium absorption and has potential implications in exocrine function and cancer therapy.
- ECaC is critical for calcium homeostasis in the kidney.