| 1. |
- Fenton, Robert A., et al.
(author)
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Differential water permeability and regulation of three aquaporin 4 isoforms
- 2010
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In: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 67:5, s. 829-840
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Journal article (peer-reviewed)abstract
- Aquaporin 4 (AQP4) is expressed in the perivascular glial endfeet and is an important pathway for water during formation and resolution of brain edema. In this study, we examined the functional properties and relative unit water permeability of three functional isoforms of AQP4 expressed in the brain (M1, M23, Mz). The M23 isoform gave rise to square arrays when expressed in Xenopus laevis oocytes. The relative unit water permeability differed significantly between the isoforms in the order of M1 > Mz > M23. None of the three isoforms were permeable to small osmolytes nor were they affected by changes in external K+ concentration. Upon protein kinase C (PKC) activation, oocytes expressing the three isoforms demonstrated rapid reduction of water permeability, which correlated with AQP4 internalization. The M23 isoform was more sensitive to PKC regulation than the longer isoforms and was internalized significantly faster. Our results suggest a specific role for square array formation.
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| 2. |
- Landegren, Nils, et al.
(author)
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Autoantibodies Targeting a Collecting Duct-Specific Water Channel in Tubulointerstitial Nephritis
- 2016
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In: Journal of the American Society of Nephrology: JASN. - 1533-3450 .- 1046-6673. ; 27:10, s. 3220-3228
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Journal article (peer-reviewed)abstract
- Tubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patients with autoimmune polyendocrine syndrome type 1 who developed tubulointerstitial nephritis and ESRD in association with autoantibodies against kidney collecting duct cells. One of the patients developed autoantibodies targeting the collecting duct-specific water channel aquaporin 2, whereas autoantibodies of the two other patients reacted against the HOXB7 or NFAT5 transcription factors, which regulate the aquaporin 2 promoter. Our findings suggest that tubulointerstitial nephritis developed in these patients as a result of an autoimmune insult on the kidney collecting duct cells.
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| 3. |
- Zelenina, Marina, et al.
(author)
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A role for AQP4 in renal K+ transport
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Other publication (other academic/artistic)abstract
- The principal cells of the collecting duct carry out two major tasks: concentration of urine and regulation of K+ homeostasis. Two water channels, AQP3 and AQP4, are expressed in the principal cell basolateral membrane. We propose that AQP4 participates in the regulation of K+ transport in the principal cells. K+ enters the cell via Na+, K+-ATPase-mediated transport in the basolateral membrane. The presence of K+ channels in this membrane permits some K+ recirculation, considered important for maintenance of membrane potential. Here we show that AQP4, but not AQP3, assembles with both Na+, K+-ATPase and an inwardly rectifying K+ channel Kir7.1. We hypothesize that AQP4, Na+, K+-ATPase and Kir7.1 form a K+-transporting microdomain and that AQP4 serves to maintain a favorable concentration gradient for K+ efflux into the diffusion-limited space within the deep infoldings in principal cell basal membrane. The hypothesis is tested in a mathematical model. The model predicts that the impact of AQP-mediated water transport on K+ transport is more significant if AQP water permeability is sensitive to fluctuations in extracellular K+ concentration ([K+]e). We measured water permeability of AQP4 expressed in a renal epithelial cell line and found that it is upregulated when [K+]e is increased to 8 mM, and downregulated when [K+]e is decreased to 1 mM. Studies in an oocyte system indicate that AQP4 does not possess a voltage or K+ sensor. Finally, we show that the expression of AQP4 in rat renal medulla is, in contrast to the expression of AQP2 and AQP3, resistant to changes in K+ intake. Our experimental data, together with the mathematical model, support the concept that AQP4 is involved in principal cell K+ transport processes.
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