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Abstract: FR-OR066

Response of Intercalated Cell (IC) BKα Knock-Out Mice to a High K (HK) Diet

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic

Authors

  • Carrisoza-Gaytan, Rolando, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Ray, Evan C., UPMC, Pittsburgh, Pennsylvania, United States
  • Marciszyn, Allison L., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Wu, Peng, New York Medical College, Valhalla, New York, United States
  • Liu, Leah, McGill University, Montreal, Quebec, Canada
  • Subramanya, Arohan R., University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Wang, WenHui, New York Medical College, Valhalla, New York, United States
  • Flores, Daniel, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Kohan, Donald E., University of Utah Health Sciences Center, Salt Lake City, Utah, United States
  • Kleyman, Thomas R., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Satlin, Lisa M., Icahn School of Medicine at Mount Sinai, New York, New York, United States
Background

Flow-induced K secretion (FIKS) in the cortical collecting duct (CCD) is mediated by BK channels, which also contribute to the renal adaptation to a high K diet (HKD). BK channels are expressed in both ICs and principal cells (PCs) in CCDs. We generated a mouse with a targeted deletion of BKα, the pore forming subunit of the BK channel, in ICs (IC-BKα-KO) by crossing floxed BKα mice with B1 V-ATPase Cre mice. Perforated cell recordings of ICs in CCDs in these KO mice revealed reduced charybdotoxin (CTX)-sensitive K currents vs. those in floxed controls, suggesting that the KO would have a limited capacity for FIKS and renal adaptation to a HKD. In fact, KO mice exhibited a higher blood [K] vs. controls (5.5±0.8 vs. 5.0±0.7 mM; p<0.05), yet rates of urinary K excretion in response to volume expansion were similar in both groups.

Methods

See results.

Results

To confirm the contribution of IC BK channels to FIKS and K adaptation, we measured net transepithelial transport (Jx, in pmol/min.mm) of Na and K, in control (n=4) and KO (n=6) microperfused CCDs from mice fed a HKD x 10 d. Similar rates of flow-stimulated JNa were observed in control and KO CCDs (43.3±6.5 and 26.9±8.3, respectively, p=NS), but FIKS, present in control CCDs (-5.0±0.6), was absent in KO tubules (-1.1±0.6; p<0.05). Although CTX-sensitive K currents in PCs were upregulated in KO mice (454±40 pA; n=6) vs. those in controls (304±28 pA; n=5; p=0.02), the failure to detect FIKS in KO CCDs underscored the critical role of ICs vs. PCs in BK channel-mediated K secretion. ROMK immunolabeling of kidney cryosections revealed a 16% increase in apical membrane relative to whole cell expression in calbindin-positive DCTs of KO mice vs. controls.

Conclusion

We conclude that in the absence of IC BKα, mice have a limited capacity for adaptation to a HKD, as evidenced by the higher blood [K], and lack of FIKS, confirming a critical role of IC BK channels in K homeostasis. We speculate that upregulation of alternate K secretory channels, including ROMK, in other segments of the nephron occurs to enable K secretion in the absence of BK channel activity in ICs.

Funding

  • NIDDK Support