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      Mice Lacking Protein Kinase C Beta Present Modest Increases in Systolic Blood Pressure and NH 4Cl-Induced Metabolic Acidosis

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          The conventional protein kinase C isoenzyme β (PKC-β) is expressed in various structures of mouse kidney. To get insights into the function, PKC-β knockout (–/–) and wild-type (+/+) mice were studied. Under basal conditions, PKC-β–/– mice exhibited a higher systolic blood pressure (in awake mice), normal plasma concentrations of Na<sup>+</sup> and K<sup>+</sup>, and normal plasma pH. Urine osmolality and 24-hour excretion of fluid, Na<sup>+</sup>, K<sup>+</sup> and albumin were not different between genotypes, but urine pH was more alkaline in PKC-β–/– mice. Inulin clearance experiments under anesthesia confirmed a higher systolic blood pressure and revealed normal glomerular filtration rate and fractional excretion of fluid, Na<sup>+</sup> and K<sup>+</sup> in PKC-β–/– mice. The ability to restrict renal Na<sup>+</sup> excretion in response to a low Na<sup>+</sup> diet was unaltered in PKC-β–/– mice. Chronic acid loading (NH<sub>4</sub>Cl) did not affect blood pH in PKC-β+/+ mice, but induced a modest metabolic acidosis in PKC-β–/– mice. In conclusion, first evidence is presented that (i) PKC-β contributes to the regulation of arterial blood pressure, and (ii) PKC-β is required for normal acid-base balance, which may relate to its expression and function in intercalated cells of the collecting duct.

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          Most cited references 19

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          Amelioration of Vascular Dysfunctions in Diabetic Rats by an Oral PKC beta Inhibitor

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            KCNQ1-dependent transport in renal and gastrointestinal epithelia.

            Mutations in the gene encoding for the K+ channel alpha-subunit KCNQ1 have been associated with long QT syndrome and deafness. Besides heart and inner ear epithelial cells, KCNQ1 is expressed in a variety of epithelial cells including renal proximal tubule and gastrointestinal tract epithelial cells. At these sites, cellular K+ ions exit through KCNQ1 channel complexes, which may serve to recycle K+ or to maintain cell membrane potential and thus the driving force for electrogenic transepithelial transport, e.g., Na+/glucose cotransport. Employing pharmacologic inhibition and gene knockout, the present study demonstrates the importance of KCNQ1 K+ channel complexes for the maintenance of the driving force for proximal tubular and intestinal Na+ absorption, gastric acid secretion, and cAMP-induced jejunal Cl- secretion. In the kidney, KCNQ1 appears dispensable under basal conditions because of limited substrate delivery for electrogenic Na+ reabsorption to KCNQ1-expressing mid to late proximal tubule. During conditions of increased substrate load, however, luminal KCNQ1 serves to repolarize the proximal tubule and stabilize the driving force for Na+ reabsorption. In mice lacking functional KCNQ1, impaired intestinal absorption is associated with reduced serum vitamin B12 concentrations, mild macrocytic anemia, and fecal loss of Na+ and K+, the latter affecting K+ homeostasis.
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              Regulation of the expression of the Cl-/anion exchanger pendrin in mouse kidney by acid-base status.

              Pendrin belongs to a superfamily of Cl-/anion exchangers and is expressed in the inner ear, the thyroid gland, and the kidney. In humans, mutations in pendrin cause Pendred syndrome characterized by sensorineural deafness and goiter. Recently pendrin has been localized to the apical side of non-type A intercalated cells of the cortical collecting duct, and reduced bicarbonate secretion was demonstrated in a pendrin knockout mouse model. To investigate a possible role of pendrin in modulating acid-base transport in the cortical collecting duct, we examined the regulation of expression of pendrin by acid-base status in mouse kidney. Mice were treated orally either with an acid or bicarbonate load (0.28 mol/L NH4Cl or NaHCO3) or received a K+-deficient diet for one week. Immunohistochemistry and Western blotting was performed. Acid-loading caused a reduction in pendrin protein expression levels within one day and decreased expression to 23% of control levels after one week. Concomitantly, pendrin protein was shifted from the apical membrane to the cytosol, and the relative abundance of pendrin positive cells declined. Similarly, in chronic K+-depletion, known to elicit a metabolic alkalosis, pendrin protein levels decreased and pendrin expression was shifted to an intracellular pool with the relative number of pendrin positive cells reduced. In contrast, following oral bicarbonate loading pendrin was found exclusively in the apical membrane and the relative number of pendrin positive cells increased. These results are in agreement with a potential role of pendrin in bicarbonate secretion and regulation of acid-base transport in the cortical collecting duct.

                Author and article information

                Kidney Blood Press Res
                Kidney and Blood Pressure Research
                S. Karger AG
                June 2006
                06 June 2006
                : 29
                : 1
                : 36-42
                aInstitute of Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany; bHuazhong University of Science and Technology, Tongji Medical College, Xiehe Hospital, Wuhan, China; cMax Planck Institute for Experimental Endocrinology, Hannover, Germany; dDepartments of Medicine and Pharmacology, University of California San Diego and VAMCSD, San Diego, Calif., USA
                92486 Kidney Blood Press Res 2006;29:36–42
                © 2006 S. Karger AG, Basel

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                Page count
                Figures: 5, References: 36, Pages: 7
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