| First Author | Tomilin V | Year | 2019 |
| Journal | Am J Physiol Renal Physiol | Volume | 316 |
| Issue | 5 | Pages | F948-F956 |
| PubMed ID | 30838874 | Mgi Jnum | J:280195 |
| Mgi Id | MGI:6369173 | Doi | 10.1152/ajprenal.00043.2019 |
| Citation | Tomilin V, et al. (2019) TRPV4 deletion protects against hypokalemia during systemic K(+) deficiency. Am J Physiol Renal Physiol 316(5):F948-F956 |
| abstractText | Tight regulation of K(+) balance is fundamental for normal physiology. Reduced dietary K(+) intake, which is common in Western diets, often leads to hypokalemia and associated cardiovascular- and kidney-related pathologies. The distal nephron, and, specifically, the collecting duct (CD), is the major site of controlled K(+) reabsorption via H(+)-K(+)-ATPase in the state of dietary K(+) deficiency. We (Mamenko MV, Boukelmoune N, Tomilin VN, Zaika OL, Jensen VB, O'Neil RG, Pochynyuk OM. Kidney Int 91: 1398-1409, 2017) have previously demonstrated that the transient receptor potential vanilloid type 4 (TRPV4) Ca(2+) channel, abundantly expressed in the CD, contributes to renal K(+) handling by promoting flow-induced K(+) secretion. Here, we investigated a potential role of TRPV4 in controlling H(+)-K(+)-ATPase-dependent K(+) reabsorption in the CD. Treatment with a K(+)-deficient diet (<0.01% K(+)) for 7 days reduced serum K(+) levels in wild-type (WT) mice from 4.3 +/- 0.2 to 3.3 +/- 0.2 mM but not in TRPV4(-/-) mice (4.3 +/- 0.1 and 4.2 +/- 0.3 mM, respectively). Furthermore, we detected a significant reduction in 24-h urinary K(+) levels in TRPV4(-/-) compared with WT mice upon switching to K(+)-deficient diet. TRPV4(-/-) animals also had significantly more acidic urine on a low-K(+) diet, but not on a regular (0.9% K(+)) or high-K(+) (5% K(+)) diet, which is consistent with increased H(+)-K(+)-ATPase activity. Moreover, we detected a greatly accelerated H(+)-K(+)-ATPase-dependent intracellular pH extrusion in freshly isolated CDs from TRPV4(-/-) compared with WT mice fed a K(+)-deficient diet. Overall, our results demonstrate a novel kaliuretic role of TRPV4 by inhibiting H(+)-K(+)-ATPase-dependent K(+) reabsorption in the CD. We propose that TRPV4 inhibition could be a novel strategy to manage certain hypokalemic states in clinical settings. |
