ArticleThe Journal of biological chemistry2013
Discrete control of TRPV4 channel function in the distal nephron by protein kinases A and C.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- The mechanosensitive channel TRPV4 inhibits pulmonary inflammation by limiting NF-κB signaling in alveolar macrophages.Science signaling · 2025Article
- Mechanosensitive ion channels and inflammation: key links in cellular signal transduction.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Insulin potentiates mechanical responses in small dorsal root ganglion neurons by increasing the sensitization of TRPV4 channels.American journal of physiology. Cell physiology · 2025Article
- Functions of TRPs in retinal tissue in physiological and pathological conditions.Frontiers in molecular neuroscience · 2024Review
- Consideration of Kinase Inhibitors for the Treatment of Hydrocephalus.International journal of molecular sciences · 2023Review
- TRPV4 functional status in cystic cells regulates cystogenesis in autosomal recessive polycystic kidney disease during variations in dietary potassium.Physiological reports · 2023Article
- Characterization of TRPV4-mediated signaling pathways in an optimized human choroid plexus epithelial cell line.American journal of physiology. Cell physiology · 2022Article
- Following Ussing's legacy: from amphibian models to mammalian kidney and brain.American journal of physiology. Cell physiology · 2022Review
- Functional Interaction between Transient Receptor Potential V4 Channel and Neuronal Calcium Sensor 1 and the Effects of Paclitaxel.Molecular pharmacology · 2021Article
- With-No-Lysine Kinase 1 (WNK1) Augments TRPV4 Function in the Aldosterone-Sensitive Distal Nephron.Cells · 2021Article
- Comprehensive gene expression profiling of human astrocytes treated with a hepatic encephalopathy-inducible factor, alpha 1-antichymotripsin.Biochemistry and biophysics reports · 2020Article
- Adenosine inhibits the basolateral ClAmerican journal of physiology. Renal physiology · 2020Article
- Urinary concentrating defect in mice lacking Epac1 or Epac2.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 Channels.Frontiers in pharmacology · 2019Article
- TRPC3 determines osmosensitive [Ca2+]i signaling in the collecting duct and contributes to urinary concentration.PloS one · 2019Article
- Deficient transient receptor potential vanilloid type 4 function contributes to compromised [CaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- The renal TRPV4 channel is essential for adaptation to increased dietary potassium.Kidney international · 2017Article
- Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes Insipidus.Journal of the American Society of Nephrology : JASN · 2016Article
- Adrenergic activation attenuates astrocyte swelling induced by hypotonicity and neurotrauma.Glia · 2016Article
- Role of renal TRP channels in physiology and pathology.Seminars in immunopathology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
We have recently documented that the Ca(2+)-permeable TRPV4 channel, which is abundantly expressed in distal nephron cells, mediates cellular Ca(2+) responses to elevated luminal flow. In this study, we combined Fura-2-based [Ca(2+)]i imaging with immunofluorescence microscopy in isolated split-opened distal nephrons of C57BL/6 mice to probe the molecular determinants of TRPV4 activity and subcellular distribution. We found that activation of the PKC pathway with phorbol 12-myristate 13-acetate significantly increased [Ca(2+)]i responses to flow without affecting the subcellular distribution of TRPV4. Inhibition of PKC with bisindolylmaleimide I diminished cellular responses to elevated flow. In contrast, activation of the PKA pathway with forskolin did not affect TRPV4-mediated [Ca(2+)]i responses to flow but markedly shifted the subcellular distribution of the channel toward the apical membrane. These actions were blocked with the specific PKA inhibitor H-89. Concomitant activation of the PKA and PKC cascades additively enhanced the amplitude of flow-induced [Ca(2+)]i responses and greatly increased basal [Ca(2+)]i levels, indicating constitutive TRPV4 activation. This effect was precluded by the selective TRPV4 antagonist HC-067047. Therefore, the functional status of the TRPV4 channel in the distal nephron is regulated by two distinct signaling pathways. Although the PKA-dependent cascade promotes TRPV4 trafficking and translocation to the apical membrane, the PKC-dependent pathway increases the activity of the channel on the plasma membrane.
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Registered trials
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