Abstract
Background
The calcium (Ca)-activated potassium (K) channel is an alternative K-secretory pathway in the apical membranes of the distal nephrons of adrenalectomized (ADX) animals. As a potential approach for estimating intracellular Ca2+ increase, we investigated normal and ADX mice to determine whether dietary K intake would stimulate the expression of the calbindin D28k protein, a cytosolic Ca2+-binding protein, along the distal nephron consisting of the early and late portions of the distal convoluted tubule (DCT1 and DCT2, respectively), the CNT, and CCD.
Methods
ADX mice received a control diet plus either 0.3% NaCl solution (C) or a 0.3% NaCl plus 3% KCl solution (HK) for 7 days before the experiment.
Results
The mean plasma K concentration and pH were significantly (P < 0.001) higher (7.9 ± 0.3 mEq/l) and lower (7.28 ± 0.02) in the K-loaded ADX mice than in the control ADX mice. The mean urinary K excretion (mEq/day) and urine flow (ml/day) increased significantly (P < 0.0001) from 0.47 ± 0.07 (C) to 4.80 ± 0.57 (HK) and from 1.1 ± 0.2 (C) to 8.8 ± 1.0 (HK). Urinary Ca excretion significantly (P < 0.005 and P < 0.05, respectively) increased in K-loaded normal and ADX mice compared with control normal and ADX mice. Immunofluorescence studies revealed that the relative staining of calbindin was 167.0 ± 15.4%, 291.3 ± 13.8%, and 206.3 ± 11.3% for DCT1, DCT2/CNT, and CCD of normal control mice, respectively. These values increased significantly (P < 0.0001) only in DCT2/CNT (574.8 ± 42%) of the K-loaded ADX mice.
Conclusion
Upregulation of calbindin in the late distal tubule suggests that Ca2+-dependent K transport may function as an alternative mechanism for urinary K excretion in ADX mice.
Similar content being viewed by others
References
Reilly RF, Ellison DH. Mammalian distal tubule: physiology, pathophysiology, and molecular anatomy. Physiol Rev. 2000;80:277–313.
Giebisch G, Hebert SC, Wang WH. New aspects of renal potassium transport. Pflügers Arch. 2003;446:289–97.
Ho K, Nichols CG, Lederer WJ, Lytton J, Vassilev PM, Kanazirska MV, et al. Cloning and expression of an inwardly rectifying ATP-regulated potassium channel. Nature (Lond). 1993;362:31–8.
Frindt G, Shah A, Edvinsson J, Palmer LG. Dietary K regulates ROMK channels in connecting tubule and cortical collecting duct of rat kidney. Am J Physiol. 2009;296:F347–54.
Frindt G, Palmer LG. Effects of dietary K on cell-surface expression of renal ion channels and transporters. Am J Physiol. 2010;299:F890–7.
Grimm PR, Sansom SC. BK channels in the kidney. Curr Opin Nephrol Hypertens. 2007;16:430–6.
Muto S, Sansom S, Giebisch G. Effects of a high potassium diet on electrical properties of cortical collecting ducts from adrenalectomized rabbits. J Clin Invest. 1988;81:376–80.
Wingo CS, Seldin DW, Kokko JP, Jacobson HR. Dietary modulation of active potassium secretion in the cortical collecting tubule of adrenalectomized rabbits. J Clin Invest. 1982;70:579–86.
Amorim JB, Musa-Aziz R, Mello-Aires M, Malnic G. Signaling path of the action of AVP on distal K+ secretion. Kidney Int. 2004;66:696–704.
Bailey MA, Cantone A, Yan Q, MacGregor GG, Leng Q, Amorim JB, et al. Maxi-K channels contribute to urinary potassium excretion in the ROMK-deficient mouse model of Type II Bartter’s syndrome and in adaptation to a high-K diet. Kidney Int. 2006;70:51–9.
Liu W, Morimoto T, Woda C, Kleyman TR, Satlin LM. Ca2+ dependence of flow-stimulated K secretion in the mammalian cortical collecting duct. Am J Physiol. 2007;293:F227–35.
Tohmon M, Fukase M, Kishihara M, Kadowaki S, Fujita T. Effect of glucocorticoid administration on intestinal, renal, and cerebellar calbindin-D28K in chicks. J Bone Miner Res. 1988;3:325–31.
Hemmingsen C. Regulation of renal calbindin-D28K. Pharmacol Toxicol. 2000;87(Suppl 3):5–30.
Taylor AN, McIntosh JE, Bourdeau JE. Immunocytochemical localization of vitamin D-dependent calcium-binding protein in renal tubules of rabbit, rat, and chick. Kidney Int. 1982;21:765–73.
Rizzo M, Capasso G, Bleich M, Pica A, Grimaldi D, Bindels RJ, et al. Effect of chronic metabolic acidosis on calbindin expression along the rat distal tubule. J Am Soc Nephrol. 2000;11:203–10.
Fukagawa M, Nakanishi S, Fujii H, Hamada Y, Abe T. Regulation of parathyroid function in chronic kidney disease (CKD). Clin Exp Nephrol. 2006;10:175–9.
Nakai K, Komaba H, Fukagawa M. New insights into the role of fibroblast growth factor 23 in chronic kidney disease. J Nephrol. 2010;23:619–25.
Boros S, Bindels RJ, Hoenderop JGJ. Active Ca2+ reabsorption in the connecting tubule. Pflügers Arch. 2009;458:99–109.
Armbrecht HJ, Boltz M, Strong R, Richardson A, Bruns ME, Christakos S. Expression of calbindin-D decreases with age in intestine and kidney. Endocrinology. 1989;125:2950–6.
Kawahara K, Anzai N. Potassium transport and potassium channels in the kidney tubules. Jpn J Physiol. 1997;47:1–10.
Rizzo M, Metafora S, Morelli F, Russo F, Ciani F, Capasso G. Chronic administration of bumetanide upregulates calbindin D28k mRNA and protein abundance in rat distal convoluted tubules. Nephron Physiol. 2004;97:16–22.
Yang SS, Hsu YJ, Chiga M, Rai T, Sasaki S, Uchida S, et al. Mechanisms for hypercalciuria in pseudohypoaldosteronism type II-causing WNK4 knock-in mice. Endocrinology. 2010;151:1829–36.
Sandulache D, Grahammer F, Artunc F, Henke G, Hussain A, Nasir O, et al. Renal Ca2+ handling in sgk1 knockout mice. Pflügers Arch. 2006;452:444–52.
Yang CW, Kim J, Kim YH, Cha JH, Mim SY, Kim YO, et al. Inhibition of calbindin D28K expression by cyclosporin A in rat kidney: the possible pathogenesis of cyclosporin A-induced hypercalciuria. J Am Soc Nephrol. 1998;9:1416–26.
Lee CT, Huynh VM, Lai LW, Lien YH. Cyclosporine A-induced hypercalciuria in calbindin-D28k knockout and wild-type mice. Kidney Int. 2002;62:2055–61.
Krapf R, Seldin DW, Alpern RJ. Clinical syndromes of metabolic acidosis. In: Alpern RJ, Hebert SC, editors. The kidney: physiology and pathophysiology. Amsterdam: Academic; 2008. p. 1667–720.
Giebisch G, Windhager E. Transport of potassium by the tubules. In: Boron WF, Boulpaep EL, editors. Medical physiology. Philadelphia: Saunders; 2003. p. 814–27.
Ikeda M, Yoshitomi K, Imai M, Kurokawa K. Cell Ca2+ response to luminal vasopressin in cortical collecting tubule principal cells. Kidney Int. 1994;45:811–6.
Dubrovsky AH, Nair RC, Byers MK, Levine DZ. Renal net acid excretion in the adrenalectomized rat. Kidney Int. 1981;19:516–28.
Kinsella J, Cujdik T, Sacktor B. Na+–H+ exchange activity in renal brush border membrane vesicles in response to metabolic acidosis: the role of glucocorticoids. Proc Natl Acad Sci USA. 1984;81:630–4.
Matsuda O, Nonoguchi H, Tomita K, Shiigai T, Ida T, Shinohara S, et al. Primary role of hyperkalemia in the acidosis of hyporeninemic hypoaldosteronism. Nephron. 1988;49:203–9.
Sebastian A, Schambelan M, Lindenfeld S, Morris RC Jr. Amelioration of metabolic acidosis with fludrocortisone therapy in hyporeninemic hypoaldosteronism. N Engl J Med. 1977;297:576–83.
Pela I, Gasperini S, Pasquini E, Donati MA. Hyperkalemia after acute metabolic decompensation in two children with vitamin B12-unresponsive methylmalonic acidemia and normal renal function. Clin Nephrol. 2006;66:63–6.
Bushinsky DA, Parker WR, Alexander KM, Krieger NS. Metabolic, but not respiratory, acidosis increases bone PGE2 levels and calcium release. Am J Physiol. 2001;281:F1058–66.
Lambers TT, Oancea E, de Groot T, Topala CN, Hoenderop JG, Bindels RJ. Extracellular pH dynamically controls cell surface delivery of functional TRPV5 channels. Mol Cell Biol. 2007;27:1486–94.
Zhai XY, Thomsen JS, Birn H, Kristoffersen IB, Andreasen A, Christensen EI. Three-dimensional reconstruction of the mouse nephron. J Am Soc Nephrol. 2006;17:77–88.
Acknowledgments
This study was supported by grants from Research Projects of the Kitasato University GSMS to K. K. (2008, 2009) and H. K. (2006, 2007) and from The Salt Science Research Foundation (nos. 0635, 0727). We thank Dr. H. Nonoguchi (Hyogo College Med., Nephrology) for providing helpful comments. Special thanks are extended to Y. Nakabayashi for her technical assistance. Parts of this study were presented at the meetings of the ISN/Nexus 2010 (Kyoto). The Kidney and Vascular System: Emerging Culprits in Pathogenesis and Advances in Therapy (p102) and The XXXVI IUPS 2009 (Kyoto) (J Physiol Sci 2009; 59 (Suppl): 485). Pacific Edit reviewed the manuscript before submission.
Author information
Authors and Affiliations
Corresponding author
Additional information
M. Kobayashi and Y. Yasuoka contributed equally to this work.
About this article
Cite this article
Kobayashi, M., Yasuoka, Y., Sato, Y. et al. Upregulation of calbindin D28k in the late distal tubules in the potassium-loaded adrenalectomized mouse kidney. Clin Exp Nephrol 15, 355–362 (2011). https://doi.org/10.1007/s10157-011-0414-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10157-011-0414-4