TRPV4 deletion protects against hypokalemia during systemic K+ deficiency.

TRPV4 deletion protects against hypokalemia during systemic K+ deficiency. Am J Physiol Renal Physiol. 2019 Mar 06;: Authors: Tomilin V, Mamenko M, Zaika O, Wingo CS, Pochynyuk OM Abstract 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. 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 previously demonstrated that TRPV4 Ca2+ 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 K+ deficient diet (<0.01% K+) for 7 days reduced serum K+ levels in WT mice from 4.3 ± 0.2 mM to 3.3 ± 0.2 mM, but not in TRPV4 -/- mice (4.3 ± 0.1 mM and 4.2 ± 0.3 mM, respectively). Furthermore, we detected a significant reduction in 24 h urinary K+ levels in TRPV4 -/- compared to WT mice upon switching to K+ deficient diet. TRPV4 -/- animals also had significantly more acidic urine on low K+ but not on 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 pHi extrusion in f...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research