Kidney Week

Abstract: SA-PO1010

Dietary K-Induced Temporal Changes in mRNA Encoding Proteins Associated with Renal K Secretion in Mouse

Session Information

• Fluid and Electrolytes: Basic - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid and Electrolytes

• 901 Fluid and Electrolytes: Basic

Authors

• Flores, Daniel, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Daniel Flores,

• Rein, Joshua L., Icahn School of Medicine at Mount Sinai, New York, New York, United States

Joshua L. Rein,

• Carrisoza-Gaytan, Rolando, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Rolando Carrisoza-Gaytan,

• Subramanya, Arohan R., University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Arohan R. Subramanya,

• Kleyman, Thomas R., University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Thomas R. Kleyman,

• Satlin, Lisa M., Icahn School of Medicine at Mount Sinai, New York, New York, United States

Lisa M. Satlin,

Background

Flow-induced K secretion in the cortical collecting duct (CCD) of the distal nephron is mediated by Ca²⁺/stretch-activated BK channels, which also contribute to the renal adaptation to a high K diet (HKD). We reported that CCDs from rabbits fed a HKD for 10 d exhibit an increase in steady-state abundance of BK channel subunit-specific mRNAs and expression of immunodetectable BKα and L-WNK1 expression in the apical membrane of β-type intercalated cells (ICs). Overexpression of L-WNK1 increases BKα whole cell abundance and functional channel expression in HEK cells suggesting that an increase in L-WNK1 in ICs may mediate enhanced BK channel expression and K secretion in K-adapted CCDs. We sought to examine the temporal changes in mRNA abundance of BK channel subunits and L-WNK1 as well as other major CCD transport and regulatory proteins in mouse kidney following initiation of HKD or low K diet (LKD).

Methods

C57BL/6 mice on a control K diet were switched to either a HKD or LKD for up to 11 days. On the day of sacrifice, spot blood and urine samples were collected for measurement of [Na] and [K] by flame photometry. qPCR primers and probes specific for BKα, β1, β4, and γ subunits and for regulatory kinases L-WNK1, KS-WNK1, and WNK4 were used to assess message abundance in renal cortical homogenates.

Results

Steady state expression of BKα mRNA increased >3-fold by day 7 of HKD (n=4, p<0.05) but did not significantly change during LKD. No significant changes were observed for message encoding BK β1, β4, γ subunits or L-WNK1, KS-WNK1, and WNK4 during either diet. Plasma [Na] and [K] remained unchanged under HKD and LKD, while urine [K] increased during HKD and decreased during LDK.

Conclusion

HKD increased steady state abundance of message encoding BKα. The failure to detect an increase in message encoding WNK1, a regulatory protein known to increase BK channel expression during HKD, may reflect post-translational modification.

Funding

• NIDDK Support