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.
","abstract_html":"<p>The Ca<sup>2+</sup>-permeable TRPV4 channel is predominantly expressed in the distal nephron (DN) and its activity is essential for [Ca<sup>2+</sup>]<sub>i</sub> 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<sup>+</sup> diet (5%) and decreased by dietary K<sup>+</sup> restriction (0.003%). In contrast, variations in Na<sup>+</sup> regimen had no apparent effect on TRPV4 expression and mRNA levels. Regulation of TRPV4 protein expression by K<sup>+</sup> 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<sup>+</sup> and Na<sup>+</sup> intake resulted in redistribution of the channel towards the apical plasma membrane of DN cells, while K<sup>+</sup> and Na<sup>+ </sup>restrictions caused cytosolic distribution of TRPV4. Augmented TRPV4 expression and localization to the apical plasma membrane during high K<sup>+</sup> and Na<sup>+</sup> intake were associated with significantly augmented flow-induced [Ca<sup>2+</sup>]<sub>i</sub> responses in DN cells. In summary, my findings demonstrate that high K<sup>+</sup> and Na<sup>+</sup> 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<sup>+</sup> and Na<sup>+ </sup>balance contributing to cardiovascular abnormalities.</p>","abstract_has_math":false,"creators":["Boukelmoune, Nabila"],"institution":null,"degree_name":"Masters of Science (MS)","degree_level":"Thesis (MS)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Oleh Pochynyuk","Roger.G.O’Neil","Kartik Venkatachalam"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-12-01T08:00:00Z","date_published":"2014-12-01T08:00:00Z","updated_at":"2026-07-24T05:49:41Z","subjects":["TRPV4","mechanosensitivity","calcium","tubular flow","distal nephron","potassium diet","sodium diet","ion channels","Cellular and Molecular Physiology","Physiology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/538","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Oleh Pochynyuk","Roger.G.O’Neil","Kartik Venkatachalam"]},{"key":"dc:creator","label":"Author","values":["Boukelmoune, Nabila"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2015-12-19T08:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis (MS)"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Masters of Science (MS)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["TRPV4","mechanosensitivity","calcium","tubular flow","distal nephron","potassium diet","sodium diet","ion channels","Cellular and Molecular Physiology","Physiology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/538"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["Regulation of Functional Expression of Mechanosensitive Trpv4 Channel In The Distal Nephron By Dietary Potassium and Sodium Intake"]}]}],"canonical_facts":{"dc:contributor":["Oleh Pochynyuk","Roger.G.O’Neil","Kartik Venkatachalam"],"dc:creator":["Boukelmoune, Nabila"],"dc:date.available":["2015-12-19T08:00:00Z"],"dc:description.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.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/538"],"dc:subject":["TRPV4","mechanosensitivity","calcium","tubular flow","distal nephron","potassium diet","sodium diet","ion channels","Cellular and Molecular Physiology","Physiology"],"dc:title":["Regulation of Functional Expression of Mechanosensitive Trpv4 Channel In The Distal Nephron By Dietary Potassium and Sodium Intake"],"thesis:degree_level":["Thesis (MS)"],"thesis:degree_name":["Masters of Science (MS)"]},"updated_at":"2026-07-24T05:49:41Z"}