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  • Review Article
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The role of transient receptor potential channels in kidney disease

Nature Reviews Nephrology volume 5, pages 441–449 (2009)Cite this article

Abstract

The transient receptor potential (TRP) superfamily consists, in mammals, of six protein subfamilies, TRPC, TRPM, TRPV, TRPA, TRPML and TRPP. TRPs are cation channels involved in many physiological processes and in the pathogenesis of various disorders. In the kidney, TRP channels are expressed along the nephron, and a role for some of these channels in renal function has been proposed. TRPC3 is thought to facilitate calcium ion influx into the principal cells of the collecting duct in response to vasopressin. TRPM3 and TRPV4 might be osmosensors, whereas the TRPP1/TRPP2 complex could function as a mechanosensor in the cilia of renal epithelial cells. A number of kidney diseases have also been linked to dysfunctional activity of TRPs. TRPC6 dysfunction has been associated with the onset of focal segmental glomerosclerosis; TRPP2 dysfunction is linked to autosomal-dominant polycystic kidney disease, TRPM6 mutations underlie hypomagnesemia with secondary hypocalcemia, and TRPV1 dysfunction is implicated in renal hypertension. A link between TRPC1 dysfunction and diabetic nephropathy has also been suggested in an animal model. Animal studies have implicated a role for TRPV5 in idiopathic hypercalciuria and vitamin D-dependent rickets, although these observations have not been confirmed in patients. This Review focuses on the role of renal TRP channels in health and disease.

Key Points

  • Transient receptor potential channels (TRPs) are a family of cation-permeable channels that, depending on the individual protein, are functional as homotetramers or heterotetramers

  • TRPs are also expressed along the nephron, and evidence is now available indicating that malfunction of these channels is involved in hereditary and acquired kidney disorders

  • Reabsorption of Ca2+ and Mg2+ in the distal part of the nephron is facilitated by the epithelial Ca2+ (TRPV5) and Mg2+ (TRPM6) channels

  • Progress in the comprehension of TRP channelopathies will stimulate the development of novel therapeutic strategies

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Figure 1: Structure of transient receptor potential proteins.
Figure 2: Transient receptor potential channel expression in the human nephron.
Figure 3: Role of TRPM6 in Mg2+ reabsorption in the distal convoluted tube.
Figure 4: Mechanosensory function of TRPP1 and TRPP2 in the distal convoluted tubule.
Figure 5: Role of TRPV5 in Ca2+ reabsorption in the distal convoluted tubule and connecting tubule.

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References

  1. Nilius, B. TRP channels in disease. Biochim. Biophys. Acta 1772, 805–812 (2007).

    CAS  PubMed  Google Scholar 

  2. Hoenderop, J. G. & Bindels, R. J. Calciotropic and magnesiotropic TRP channels. Physiology (Bethesda) 23, 32–40 (2008).

    CAS  Google Scholar 

  3. Chang, Q. et al. Molecular determinants in TRPV5 channel assembly. J. Biol. Chem. 279, 54304–54311 (2004).

    CAS  PubMed  Google Scholar 

  4. Clapham, D. E. TRP channels as cellular sensors. Nature 426, 517–524 (2003).

    CAS  PubMed  Google Scholar 

  5. Nilius, B., Owsianik, G., Voets, T. & Peters, J. A. Transient receptor potential cation channels in disease. Physiol. Rev. 87, 165–217 (2007).

    CAS  PubMed  Google Scholar 

  6. Goel, M., Sinkins, W. G., Zuo, C. D., Estacion, M. & Schilling, W. P. Identification and localization of TRPC channels in the rat kidney. Am. J. Physiol. Renal Physiol. 290, F1241–F1252 (2006).

    CAS  PubMed  Google Scholar 

  7. Goel, M., Sinkins, W. G., Zuo, C. D., Hopfer, U. & Schilling, W. P. Vasopressin-induced membrane trafficking of TRPC3 and AQP2 channels in cells of the rat renal collecting duct. Am. J. Physiol. Renal Physiol. 293, F1476–F1488 (2007).

    CAS  PubMed  Google Scholar 

  8. Groenestege, W. M., Hoenderop, J. G., van den Heuvel, L., Knoers, N. & Bindels, R. J. The epithelial Mg2+ channel transient receptor potential melastatin 6 is regulated by dietary Mg2+ content and estrogens. J. Am. Soc. Nephrol. 17, 1035–1043 (2006).

    CAS  PubMed  Google Scholar 

  9. Hanaoka, K. et al. Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents. Nature 408, 990–994 (2000).

    CAS  PubMed  Google Scholar 

  10. Wimalawansa, S. J. Calcitonin gene-related peptide and its receptors: molecular genetics, physiology, pathophysiology, and therapeutic potentials. Endocr. Rev. 17, 533–585 (1996).

    CAS  PubMed  Google Scholar 

  11. Tian, W. et al. Renal expression of osmotically responsive cation channel TRPV4 is restricted to water-impermeant nephron segments. Am. J. Physiol. Renal Physiol. 287, F17–F24 (2004).

    PubMed  Google Scholar 

  12. Strotmann, R., Harteneck, C., Nunnenmacher, K., Schultz, G. & Plant, T. D. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat. Cell Biol. 2, 695–702 (2000).

    CAS  PubMed  Google Scholar 

  13. Hoenderop, J. G. et al. Localization of the epithelial Ca(2+) channel in rabbit kidney and intestine. J. Am. Soc. Nephrol. 11, 1171–1178 (2000).

    CAS  PubMed  Google Scholar 

  14. Nijenhuis, T., Hoenderop, J. G., van der Kemp, A. W. & Bindels, R. J. Localization and regulation of the epithelial Ca2+ channel TRPV6 in the kidney. J. Am. Soc. Nephrol. 14, 2731–2740 (2003).

    CAS  PubMed  Google Scholar 

  15. Lee, N. et al. Expression and characterization of human transient receptor potential melastatin 3 (hTRPM3). J. Biol. Chem. 278, 20890–20897 (2003).

    CAS  PubMed  Google Scholar 

  16. Huang, C. L. The transient receptor potential superfamily of ion channels. J. Am. Soc. Nephrol. 15, 1690–1699 (2004).

    CAS  PubMed  Google Scholar 

  17. Du, J. et al. Canonical transient receptor potential 1 channel is involved in contractile function of glomerular mesangial cells. J. Am. Soc. Nephrol. 18, 1437–1445 (2007).

    CAS  PubMed  Google Scholar 

  18. Worley, P. F. et al. TRPC channels as STIM1-regulated store-operated channels. Cell Calcium 42, 205–211 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Abramowitz, J. & Birnbaumer, L. Physiology and pathophysiology of canonical transient receptor potential channels. FASEB J. 23, 297–328 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Giunti, S., Barit, D. & Cooper, M. E. Diabetic nephropathy: from mechanisms to rational therapies. Minerva Med. 97, 241–262 (2006).

    CAS  PubMed  Google Scholar 

  21. Jawa, A., Kcomt, J. & Fonseca, V. A. Diabetic nephropathy and retinopathy. Med. Clin. North Am. 88, 1001–1036 (2004).

    CAS  PubMed  Google Scholar 

  22. McGowan, T., McCue, P. & Sharma, K. Diabetic nephropathy. Clin. Lab. Med. 21, 111–146 (2001).

    CAS  PubMed  Google Scholar 

  23. Schäfer, S. et al. Vasopeptidase inhibition prevents nephropathy in Zucker diabetic fatty rats. Cardiovasc. Res. 60, 447–454 (2003).

    PubMed  Google Scholar 

  24. Phillips, A., Janssen, U. & Floege, J. Progression of diabetic nephropathy. Insights from cell culture studies and animal models. Kidney Blood Press. Res. 22, 81–97 (1999).

    CAS  PubMed  Google Scholar 

  25. Janssen, U., Phillips, A. O. & Floege, J. Rodent models of nephropathy associated with type II diabetes. J. Nephrol. 12, 159–172 (1999).

    CAS  PubMed  Google Scholar 

  26. Niehof, M. & Borlak, J. HNF4α and the Ca-channel TRPC1 are novel disease candidate genes in diabetic nephropathy. Diabetes 57, 1069–1077 (2008).

    CAS  PubMed  Google Scholar 

  27. Winn, M. P. et al. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science 308, 1801–1804 (2005).

    CAS  PubMed  Google Scholar 

  28. Reiser, J. et al. TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nat. Genet. 37, 739–744 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Möller, C. C. et al. Induction of TRPC6 channel in acquired forms of proteinuric kidney disease. J. Am. Soc. Nephrol. 18, 29–36 (2007).

    PubMed  Google Scholar 

  30. Vriens, J. et al. Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4. Proc. Natl Acad. Sci. USA 101, 396–401 (2004).

    CAS  PubMed  Google Scholar 

  31. Mutai, H. & Heller, S. Vertebrate and invertebrate TRPV-like mechanoreceptors. Cell Calcium 33, 471–478 (2003).

    CAS  PubMed  Google Scholar 

  32. Nilius, B., Watanabe, H. & Vriens, J. The TRPV4 channel: structure-function relationship and promiscuous gating behaviour. Pflugers Arch. 446, 298–303 (2003).

    CAS  PubMed  Google Scholar 

  33. Liedtke, W. & Friedman, J. M. Abnormal osmotic regulation in trpv4-/- mice. Proc. Natl Acad. Sci. USA 100, 13698–13703 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Suzuki, M., Mizuno, A., Kodaira, K. & Imai, M. Impaired pressure sensation in mice lacking TRPV4. J. Biol. Chem. 278, 22664–22668 (2003).

    CAS  PubMed  Google Scholar 

  35. Mizuno, A., Matsumoto, N., Imai, M. & Suzuki, M. Impaired osmotic sensation in mice lacking TRPV4. Am. J. Physiol. Cell Physiol. 285, C96–C101 (2003).

    CAS  PubMed  Google Scholar 

  36. Leipziger, J. Control of epithelial transport via luminal P2 receptors. Am. J. Physiol. Renal Physiol. 284, F419–F432 (2003).

    CAS  PubMed  Google Scholar 

  37. Gagnon, F., Dulin, N. O., Tremblay, J., Hamet, P. & Orlov, S. N. ATP-induced inhibition of Na+, K+, Cl− cotransport in Madin-Darby canine kidney cells: lack of involvement of known purinoceptor-coupled signaling pathways. J. Membr. Biol. 167, 193–204 (1999).

    CAS  PubMed  Google Scholar 

  38. Silva, G. B. & Garvin, J. L. TRPV4 mediates hypotonicity-induced ATP release by the thick ascending limb. Am. J. Physiol. Renal Physiol. 295, F1090–F1095 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Köttgen, M. et al. TRPP2 and TRPV4 form a polymodal sensory channel complex. J. Cell Biol. 182, 437–447 (2008).

    PubMed  PubMed Central  Google Scholar 

  40. Giamarchi, A. et al. The versatile nature of the calcium-permeable cation channel TRPP2. EMBO Rep. 7, 787–793 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Chubanov, V. et al. Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia. Proc. Natl Acad. Sci. USA 101, 2894–2899 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Schlingmann, K. P. et al. Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. Nat. Genet. 31, 166–170 (2002).

    CAS  PubMed  Google Scholar 

  43. Walder, R. Y. et al. Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia. Nat. Genet. 31, 171–174 (2002).

    CAS  PubMed  Google Scholar 

  44. Paunier, L., Radde, I. C., Kooh, S. W., Conen, P. E. & Fraser, D. Primary hypomagnesemia with secondary hypocalcemia in an infant. Pediatrics 41, 385–402 (1968).

    CAS  PubMed  Google Scholar 

  45. Anast, C. S., Mohs, J. M., Kaplan, S. L. & Burns, T. W. Evidence for parathyroid failure in magnesium deficiency. Science 177, 606–608 (1972).

    CAS  PubMed  Google Scholar 

  46. Schlingmann, K. P., Waldegger, S., Konrad, M., Chubanov, V. & Gudermann, T. TRPM6 and TRPM7--Gatekeepers of human magnesium metabolism. Biochim. Biophys. Acta 1772, 813–821 (2007).

    CAS  PubMed  Google Scholar 

  47. Quamme, G. A. Recent developments in intestinal magnesium absorption. Curr. Opin. Gastroenterol. 24, 230–235 (2008).

    CAS  PubMed  Google Scholar 

  48. Chubanov, V. et al. Hypomagnesemia with secondary hypocalcemia due to a missense mutation in the putative pore-forming region of TRPM6. J. Biol. Chem. 282, 7656–7667 (2007).

    CAS  PubMed  Google Scholar 

  49. Topala, C. N. et al. Molecular determinants of permeation through the cation channel TRPM6. Cell Calcium 41, 513–523 (2007).

    CAS  PubMed  Google Scholar 

  50. Li, M., Jiang, J. & Yue, L. Functional characterization of homo- and heteromeric channel kinases TRPM6 and TRPM7. J. Gen. Physiol. 127, 525–537 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Voets, T. et al. TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption. J. Biol. Chem. 279, 19–25 (2004).

    CAS  PubMed  Google Scholar 

  52. Schmitz, C. et al. The channel kinases TRPM6 and TRPM7 are functionally nonredundant. J. Biol. Chem. 280, 37763–37771 (2005).

    CAS  PubMed  Google Scholar 

  53. Groenestege, W. M. et al. Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia. J. Clin. Invest. 117, 2260–2267 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Naderi, A. S. & Reilly, R. F. Jr. Hereditary etiologies of hypomagnesemia. Nat. Clin. Pract. Nephrol. 4, 80–89 (2008).

    CAS  PubMed  Google Scholar 

  55. Jean, G. W. & Shah, S. R. Epidermal growth factor receptor monoclonal antibodies for the treatment of metastatic colorectal cancer. Pharmacotherapy 28, 742–754 (2008).

    CAS  PubMed  Google Scholar 

  56. Lin, C. C. et al. Phase I study of cetuximab, erlotinib, and bevacizumab in patients with advanced solid tumors. Cancer Chemother. Pharmacol. 63, 1065–1071 (2008).

    PubMed  Google Scholar 

  57. Guarino, M. J. et al. Dual inhibition of the epidermal growth factor receptor pathway with cetuximab and erlotinib: a phase I study in patients with advanced solid malignancies. Oncologist 14, 119–124 (2009).

    CAS  PubMed  Google Scholar 

  58. Jin, J. et al. Deletion of Trpm7 disrupts embryonic development and thymopoiesis without altering Mg2+ homeostasis. Science 322, 756–760 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Ravine, D. et al. Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1. Lancet 343, 824–827 (1994).

    CAS  PubMed  Google Scholar 

  60. Harris, P. C. & Torres, V. E. Polycystic Kidney Disease. Annu. Rev. Med. 60, 321–337 (2008).

    Google Scholar 

  61. Grantham, J. J. Clinical practice. Autosomal dominant polycystic kidney disease. N. Engl. J. Med. 359, 1477–1485 (2008).

    CAS  PubMed  Google Scholar 

  62. Rizk, D. & Chapman, A. Treatment of autosomal dominant polycystic kidney disease (ADPKD): the new horizon for children with ADPKD. Pediatr. Nephrol. 23, 1029–1036 (2008).

    PubMed  Google Scholar 

  63. Chang, M. Y. & Ong, A. C. Autosomal dominant polycystic kidney disease: recent advances in pathogenesis and treatment. Nephron Physiol. 108, 1–7 (2008).

    Google Scholar 

  64. Harris, P. C. & Torres, V. E. Understanding pathogenic mechanisms in polycystic kidney disease provides clues for therapy. Curr. Opin. Nephrol. Hypertens. 15, 456–463 (2006).

    CAS  PubMed  Google Scholar 

  65. Hateboer, N. et al. Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. Lancet 353, 103–107 (1999).

    CAS  PubMed  Google Scholar 

  66. Lu, W. et al. Late onset of renal and hepatic cysts in Pkd1-targeted heterozygotes. Nat. Genet. 21, 160–161 (1999).

    CAS  PubMed  Google Scholar 

  67. Lu, W. et al. Perinatal lethality with kidney and pancreas defects in mice with a targetted Pkd1 mutation. Nat. Genet. 17, 179–181 (1997).

    CAS  PubMed  Google Scholar 

  68. Nauli, S. M. et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet. 33, 129–137 (2003).

    CAS  PubMed  Google Scholar 

  69. Hughes, J. et al. The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains. Nat. Genet. 10, 151–160 (1995).

    CAS  PubMed  Google Scholar 

  70. Sandford, R. et al. Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains. Hum. Mol. Genet. 6, 1483–1489 (1997).

    CAS  PubMed  Google Scholar 

  71. Koulen, P. et al. Polycystin-2 is an intracellular calcium release channel. Nat. Cell Biol. 4, 191–197 (2002).

    CAS  PubMed  Google Scholar 

  72. Pak, C. Y., Oata, M., Lawrence, E. C. & Snyder, W. The hypercalciurias. Causes, parathyroid functions, and diagnostic criteria. J. Clin. Invest. 54, 387–400 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Nijenhuis, T. et al. Thiazide-induced hypocalciuria is accompanied by a decreased expression of Ca2+ transport proteins in kidney. Kidney Int. 64, 555–564 (2003).

    CAS  PubMed  Google Scholar 

  74. van Abel, M. et al. Coordinated control of renal Ca(2+) transport proteins by parathyroid hormone. Kidney Int. 68, 1708–1721 (2005).

    CAS  PubMed  Google Scholar 

  75. Kaplan, R. A., Haussler, M. R., Deftos, L. J., Bone, H. & Pak, C. Y. The role of 1α,25-dihydroxyvitamin D in the mediation of intestinal hyperabsorption of calcium in primary hyperparathyroidism and absorptive hypercalciuria. J. Clin. Invest. 59, 756–760 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Broadus, A. E., Erickson, S. B., Gertner, J. M., Cooper, K. & Dobbins, J. W. An experimental human model of 1,25-dihydroxyvitamin D-mediated hypercalciuria. J. Clin. Endocrinol. Metab. 59, 202–206 (1984).

    CAS  PubMed  Google Scholar 

  77. Hoenderop, J. G. et al. Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5. J. Clin. Invest. 112, 1906–1914 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Muller, D. et al. Epithelial Ca(2+) channel (ECAC1) in autosomal dominant idiopathic hypercalciuria. Nephrol. Dial. Transplant. 17, 1614–1620 (2002).

    PubMed  Google Scholar 

  79. Renkema, K. Y. et al. TRPV5 gene polymorphisms in renal hypercalciuria. Nephrol. Dial. Transplant. 24, 1919–1924 (2009).

    CAS  PubMed  Google Scholar 

  80. Hoenderop, J. G., De Pont, J. J., Bindels, R. J. & Willems, P. H. Hormone-stimulated Ca2+ reabsorption in rabbit kidney cortical collecting system is cAMP-independent and involves a phorbol ester-insensitive PKC isotype. Kidney Int. 55, 225–233 (1999).

    CAS  PubMed  Google Scholar 

  81. Hoenderop, J. G. & Bindels, R. J. Epithelial Ca2+ and Mg2+ channels in health and disease. J. Am. Soc. Nephrol. 16, 15–26 (2005).

    CAS  PubMed  Google Scholar 

  82. Kuro-o, M. et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390, 45–51 (1997).

    CAS  PubMed  Google Scholar 

  83. Chang, Q. et al. The β-glucuronidase klotho hydrolyzes and activates the TRPV5 channel. Science 310, 490–493 (2005).

    CAS  PubMed  Google Scholar 

  84. Lu, P., Boros, S., Chang, Q., Bindels, R. J. & Hoenderop, J. G. The β-glucuronidase klotho exclusively activates the epithelial Ca2+ channels TRPV5 and TRPV6. Nephrol. Dial. Transplant. 23, 3397–3402 (2008).

    CAS  PubMed  Google Scholar 

  85. Bianco, S. D. et al. Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene. J. Bone Miner. Res. 22, 274–285 (2007).

    CAS  PubMed  Google Scholar 

  86. Akey, J. M., Swanson, W. J., Madeoy, J., Eberle, M. & Shriver, M. D. TRPV6 exhibits unusual patterns of polymorphism and divergence in worldwide populations. Hum. Mol. Genet. 15, 2106–2113 (2006).

    CAS  PubMed  Google Scholar 

  87. Suzuki, Y. et al. Gain-of-function haplotype in the epithelial calcium channel TRPV6 is a risk factor for renal calcium stone formation. Hum. Mol. Genet. 17, 1613–1618 (2008).

    CAS  PubMed  Google Scholar 

  88. Dardenne, O., Prudhomme, J., Hacking, S. A., Glorieux, F. H. & St-Arnaud, R. Rescue of the pseudo-vitamin D deficiency rickets phenotype of CYP27B1-deficient mice by treatment with 1,25-dihydroxyvitamin D3: biochemical, histomorphometric, and biomechanical analyses. J. Bone Miner. Res. 18, 637–643 (2003).

    CAS  PubMed  Google Scholar 

  89. Malloy, P. J. & Feldman, D. Vitamin D resistance. Am. J. Med. 106, 355–370 (1999).

    CAS  PubMed  Google Scholar 

  90. Dardenne, O., Prud'homme, J., Arabian, A., Glorieux, F. H. & St-Arnaud, R. Targeted inactivation of the 25-hydroxyvitamin D(3)-1α-hydroxylase gene (CYP27B1) creates an animal model of pseudovitamin D-deficiency rickets. Endocrinology 142, 3135–3141 (2001).

    CAS  PubMed  Google Scholar 

  91. Panda, D. K., Al Kawas, S., Seldin, M. F., Hendy, G. N. & Goltzman, D. 25-hydroxyvitamin D 1α-hydroxylase: structure of the mouse gene, chromosomal assignment, and developmental expression. J. Bone Miner. Res. 16, 46–56 (2001).

    CAS  PubMed  Google Scholar 

  92. Li, Y. C., Bolt, M. J., Cao, L. P. & Sitrin, M. D. Effects of vitamin D receptor inactivation on the expression of calbindins and calcium metabolism. Am. J. Physiol. Endocrinol. Metab. 281, E558–E564 (2001).

    CAS  PubMed  Google Scholar 

  93. Van Cromphaut, S. J. et al. Duodenal calcium absorption in vitamin D receptor-knockout mice: functional and molecular aspects. Proc. Natl Acad. Sci. USA 98, 13324–13329 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Hoenderop, J. G. et al. Modulation of renal Ca2+ transport protein genes by dietary Ca2+ and 1,25-dihydroxyvitamin D3 in 25-hydroxyvitamin D3-1α-hydroxylase knockout mice. FASEB J. 16, 1398–1406 (2002).

    CAS  PubMed  Google Scholar 

  95. Weber, K., Erben, R. G., Rump, A. & Adamski, J. Gene structure and regulation of the murine epithelial calcium channels ECaC1 and 2. Biochem. Biophys. Res. Commun. 289, 1287–1294 (2001).

    CAS  PubMed  Google Scholar 

  96. Grimm, C., Kraft, R., Sauerbruch, S., Schultz, G. & Harteneck, C. Molecular and functional characterization of the melastatin-related cation channel TRPM3. J. Biol. Chem. 278, 21493–21501 (2003).

    CAS  PubMed  Google Scholar 

  97. Oberwinkler, J., Lis, A., Giehl, K. M., Flockerzi, V. & Philipp, S. E. Alternative splicing switches the divalent cation selectivity of TRPM3 channels. J. Biol. Chem. 280, 22540–22548 (2005).

    CAS  PubMed  Google Scholar 

  98. Wagner, T. F. et al. Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic beta cells. Nat. Cell Biol. 10, 1421–1430 (2008).

    CAS  PubMed  Google Scholar 

  99. Valenti, G., Procino, G., Tamma, G., Carmosino, M. & Svelto, M. Minireview: aquaporin 2 trafficking. Endocrinology 146, 5063–5070 (2005).

    CAS  PubMed  Google Scholar 

  100. Kim, J. Y. et al. Homer 1 mediates store- and inositol 1,4,5-trisphosphate receptor-dependent translocation and retrieval of TRPC3 to the plasma membrane. J. Biol. Chem. 281, 32540–32549 (2006).

    CAS  PubMed  Google Scholar 

  101. Kopp, U. C., Cicha, M. Z. & Smith, L. A. Dietary sodium loading increases arterial pressure in afferent renal-denervated rats. Hypertension 42, 968–973 (2003).

    CAS  PubMed  Google Scholar 

  102. Wang, Y. & Wang, D. H. A novel mechanism contributing to development of Dahl salt-sensitive hypertension: role of the transient receptor potential vanilloid type 1. Hypertension 47, 609–614 (2006).

    CAS  PubMed  Google Scholar 

  103. Wang, Y., Babánková, D., Huang, J., Swain, G. M. & Wang, D. H. Deletion of transient receptor potential vanilloid type 1 receptors exaggerates renal damage in deoxycorticosterone acetate-salt hypertension. Hypertension 52, 264–270 (2008).

    PubMed  Google Scholar 

  104. Koomans, H. A., Blankestijn, P. J. & Joles, J. A. Sympathetic hyperactivity in chronic renal failure: a wake-up call. J. Am. Soc. Nephrol. 15, 524–537 (2004).

    PubMed  Google Scholar 

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Acknowledgements

The authors thank Dr J. Schoeber for critically reading the manuscript. This work was financially supported, in part, by grants from the Dutch Kidney Foundation (C03.6017, C06.2170) and the Netherlands Organization for Scientific Research (NWO-ALW 814.02.001, NWO-ALW 816.02.003, NWO-CW 700.55.302, ZonMw 9120.6110). J. G. J. Hoenderop is supported by an EURYI award.

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  1. Department of Physiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    Titia E. Woudenberg-Vrenken, René J. M. Bindels & Joost G. J. Hoenderop

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Woudenberg-Vrenken, T., Bindels, R. & Hoenderop, J. The role of transient receptor potential channels in kidney disease. Nat Rev Nephrol 5, 441–449 (2009). https://doi.org/10.1038/nrneph.2009.100

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