| First Author | Stavniichuk A | Year | 2023 |
| Journal | Am J Physiol Renal Physiol | Volume | 324 |
| Issue | 6 | Pages | F603-F616 |
| PubMed ID | 37141145 | Mgi Jnum | J:339087 |
| Mgi Id | MGI:7519254 | Doi | 10.1152/ajprenal.00278.2022 |
| Citation | Stavniichuk A, et al. (2023) TRPV4 expression in the renal tubule is necessary for maintaining whole body K(+) homeostasis. Am J Physiol Renal Physiol 324(6):F603-F616 |
| abstractText | The Ca(2+)-permeable transient receptor potential vanilloid type 4 (TRPV4) channel serves as the sensor of tubular flow, thus being well suited to govern mechanosensitive K(+) transport in the distal renal tubule. Here, we directly tested whether the TRPV4 function is significant in affecting K(+) balance. We used balance metabolic cage experiments and systemic measurements with different K(+) feeding regimens [high (5% K(+)), regular (0.9% K(+)), and low (<0.01% K(+))] in newly created transgenic mice with selective TRPV4 deletion in the renal tubule (TRPV4(fl/fl)-Pax8Cre) and their littermate controls (TRPV4(fl/fl)). Deletion was verified by the absence of TRPV4 protein expression and lack of TRPV4-dependent Ca(2+) influx. There were no differences in plasma electrolytes, urinary volume, and K(+) levels at baseline. In contrast, plasma K(+) levels were significantly elevated in TRPV4(fl/fl)-Pax8Cre mice on high K(+) intake. K(+)-loaded knockout mice exhibited lower urinary K(+) levels than TRPV4(fl/fl) mice, which was accompanied by higher aldosterone levels by day 7. Moreover, TRPV4(fl/fl)-Pax8Cre mice had more efficient renal K(+) conservation and higher plasma K(+) levels in the state of dietary K(+) deficiency. H(+)-K(+)-ATPase levels were significantly increased in TRPV4(fl/fl)-Pax8Cre mice on a regular diet and especially on a low-K(+) diet, pointing to augmented K(+) reabsorption in the collecting duct. Consistently, we found a significantly faster intracellular pH recovery after intracellular acidification, as an index of H(+)-K(+)-ATPase activity, in split-opened collecting ducts from TRPV4(fl/fl)-Pax8Cre mice. In summary, our results demonstrate an indispensable prokaliuretic role of TRPV4 in the renal tubule in controlling K(+) balance and urinary K(+) excretion during variations in dietary K(+) intake. NEW & NOTEWORTHY The mechanoactivated transient receptor potential vanilloid type 4 (TRPV4) channel is expressed in distal tubule segments, where it controls flow-dependent K(+) transport. Global TRPV4 deficiency causes impaired adaptation to variations in dietary K(+) intake. Here, we demonstrate that renal tubule-specific TRPV4 deletion is sufficient to recapitulate the phenotype by causing antikaliuresis and higher plasma K(+) levels in both states of K(+) load and deficiency. |
