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Mammalian Transient Receptor Potential (TRP) Cation Channels pp 321–357Cite as

TRPV5: A Ca2+ Channel for the Fine-Tuning of Ca2+ Reabsorption

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 222))

Abstract

TRPV5 is one of the two channels in the TRPV family that exhibit high selectivity to Ca2+ ions. TRPV5 mediates Ca2+ influx into cells as the first step to transport Ca2+ across epithelia. The specialized distribution in the distal tubule of the kidney positions TRPV5 as a key player in Ca2+ reabsorption. The responsiveness in expression and/or activity of TRPV5 to hormones such as 1,25-dihydroxyvitamin D3, parathyroid hormone, estrogen, and testosterone makes TRPV5 suitable for its role in the fine-tuning of Ca2+ reabsorption. This role is further optimized by the modulation of TRPV5 trafficking and activity via its binding partners; co-expressed proteins; tubular factors such as calbindin-D28k, calmodulin, klotho, uromodulin, and plasmin; extracellular and intracellular factors such as proton, Mg2+, Ca2+, and phosphatidylinositol-4,5-bisphosphate; and fluid flow. These regulations allow TRPV5 to adjust its overall activity in response to the body’s demand for Ca2+ and to prevent kidney stone formation. A point mutation in mouse Trpv5 gene leads to hypercalciuria similar to Trpv5 knockout mice, suggesting a possible role of TRPV5 in hypercalciuric disorders in humans. In addition, the single nucleotide polymorphisms in Trpv5 gene prevalently present in African descents may contribute to the efficient renal Ca2+ reabsorption among African descendants. TRPV5 represents a potential therapeutic target for disorders with altered Ca2+ homeostasis.

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Acknowledgments

We thank our colleagues Yi Jiang, Wei Zhang, Guojin Wu, and Haiyan Jiang for their contribution to our understanding of TRPV5 and TRPV6 through research and discussion. The research in our laboratory was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK072154) and the American Heart Association (0430125N, 09GRNT2160024, and 09POST2160010).

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Authors and Affiliations

  1. Cell Collection and Research Center, Institute for Biological Product Control, National Institutes for Food and Drug Control, Beijing, China

    Tao Na

  2. Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, ZRB 634, 1900 University Boulevard, Birmingham, AL, 35294-0006, USA

    Ji-Bin Peng

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  2. Ji-Bin Peng
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Correspondence to Ji-Bin Peng .

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  1. Laboratory Ion Channel Research Campus Gasthuisberg, KU Leuven Department Cell Mol Medicin, Leuven, Belgium

    Bernd Nilius

  2. Institut für Experimentelle u. Klinische, Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg, Saarland, Germany

    Veit Flockerzi

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Na, T., Peng, JB. (2014). TRPV5: A Ca2+ Channel for the Fine-Tuning of Ca2+ Reabsorption. In: Nilius, B., Flockerzi, V. (eds) Mammalian Transient Receptor Potential (TRP) Cation Channels. Handbook of Experimental Pharmacology, vol 222. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-54215-2_13

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