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

Author

• Nabila Boukelmoune, The University of Texas Graduate School of Biomedical Sciences at HoustonFollow

Date of Graduation

12-2014

Document Type

Thesis (MS)

Program Affiliation

Biomedical Sciences

Degree Name

Masters of Science (MS)

Advisor/Committee Chair

Oleh Pochynyuk

Committee Member

Roger.G.O’Neil

Committee Member

Kartik Venkatachalam

Committee Member

Richard.B.Clark

Committee Member

Peter. A. Doris

Abstract

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.

Recommended Citation

Boukelmoune, Nabila, "Regulation of Functional Expression of Mechanosensitive Trpv4 Channel In The Distal Nephron By Dietary Potassium and Sodium Intake" (2014). Dissertations and Theses (Open Access). 538.
https://digitalcommons.library.tmc.edu/utgsbs_dissertations/538

Keywords

TRPV4, mechanosensitivity, calcium, tubular flow, distal nephron, potassium diet, sodium diet, ion channels