Regulation of Functional Expression of Mechanosensitive Trpv4 Channel In The Distal Nephron By Dietary Potassium and Sodium Intake

<p>The Ca²⁺-permeable TRPV4 channel is predominantly expressed in the distal nephron (DN) and its activity is essential for [Ca²⁺]_i elevations in response to increased tubular flow. Here, I probed the physiological mechanisms controlling TRPV4 function and expression in the DN. I found that renal TRPV4 expression and mRNA levels were significantly increased by high K⁺ diet (5%) and decreased by dietary K⁺ restriction (0.003%). In contrast, variations in Na⁺ regimen had no apparent effect on TRPV4 expression and mRNA levels. Regulation of TRPV4 protein expression by K⁺ diet was independent of aldosterone action, since saturation of systemic mineralocorticoid signaling with DOCA, a precursor of aldosterone, had little effect on TRPV4 protein abundance in the kidney. Confocal immunofluorescence in split-opened DNs showed that high K⁺ and Na⁺ intake resulted in redistribution of the channel towards the apical plasma membrane of DN cells, while K⁺ and Na⁺restrictions caused cytosolic distribution of TRPV4. Augmented TRPV4 expression and localization to the apical plasma membrane during high K⁺ and Na⁺ intake were associated with significantly augmented flow-induced [Ca²⁺]_i responses in DN cells. In summary, my findings demonstrate that high K⁺ and Na⁺ intake regulate TRPV4 status to properly respond to elevated tubular flow during these physiological stimuli. I also propose that impaired regulation of TRPV4 in the DN during variations in dietary intake may result in systemic defects in K⁺ and Na⁺balance contributing to cardiovascular abnormalities.</p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2014

Author dc:creator

• Boukelmoune, Nabila

Contributors dc:contributor

• Oleh Pochynyuk
• Roger.G.O’Neil
• Kartik Venkatachalam

• TRPV4
• mechanosensitivity
• calcium
• tubular flow
• distal nephron
• potassium diet
• sodium diet
• ion channels
• Cellular and Molecular Physiology
• Physiology

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/538

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1576