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TRPV4 function in the distal nephron is regulated by dietary potassium and sodium intake (892.2)
Author(s) -
Boukelmoune Nabila,
Mamenko Mykola,
Zaika Oleg,
O'Neil Roger,
Pochynyuk Oleh
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.892.2
Subject(s) - nephron , potassium , endocrinology , medicine , sodium , chemistry , trpv4 , hyperkalemia , aldosterone , renal function , ion channel , receptor , organic chemistry
It becomes recognized that Ca 2+ ‐permeable TRPV4 channel is predominantly expressed in the distal nephron and its activity is essential for [Ca 2+ ] i elevations in response to increased tubular flow. Here, we probe whether TRPV4 function in the kidney is regulated by dietary intake of major electrolytes. We found that renal TRPV4 expression was increased by high potassium diet (5% K + ) and decreased by dietary potassium restriction (0.003 % K + ). Saturation of systemic mineralocorticoid status with DOCA had little effect on TRPV4 protein abundance pointing to an aldosterone‐independent nature of this regulation. Increased TRPV4 expression by high potassium intake was associated with significantly augmented [Ca 2+ ] i responses to elevated flow as was detected using Fura‐2 Ca 2+ imaging in freshly isolated split‐opened distal nephrons. Furthermore, dietary sodium load (2% Na + ) similarly increased renal TRPV4 expression and enhanced flow‐induced [Ca 2+ ] i responses in distal nephron cells. Interestingly, protein levels of other Ca 2+ ‐permeable channel, TRPC3, also expressed in the distal nephron, were not altered by variations in dietary potassium and sodium intake. We conclude that increased ultrafiltrate delivery to the distal nephron as a result of high potassium and sodium intake elicits respective augmentation of TRPV4 expression and therefore enhanced cellular responses to distal tubular flow. Grant Funding Source : DK095029