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Kidney Week

Abstract: FR-OR24

PIEZO1 Channels Are Necessary for BK Channel-Mediated Flow-Induced K+ Secretion (FIKS) in the Cortical Collecting Duct (CCD)

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • Carrisoza-Gaytan, Rolando, Icahn School of Medicine at Mount Sinai Department of Pediatrics, New York, New York, United States
  • Mutchler, Stephanie, University of Pittsburgh Department of Medicine, Pittsburgh, Pennsylvania, United States
  • Dalghi, Marianela G., University of Pittsburgh Department of Medicine, Pittsburgh, Pennsylvania, United States
  • Carattino, Francisco, Icahn School of Medicine at Mount Sinai Department of Pediatrics, New York, New York, United States
  • Apodaca, Gerard, University of Pittsburgh Department of Medicine, Pittsburgh, Pennsylvania, United States
  • Kleyman, Thomas R., University of Pittsburgh Department of Medicine, Pittsburgh, Pennsylvania, United States
  • Satlin, Lisa M., Icahn School of Medicine at Mount Sinai Department of Pediatrics, New York, New York, United States
Background

BK channel-mediated FIKS in intercalated cells (IC) of the CCD requires an elevation in intracellular calcium concentration [Ca2+]i triggered by hydrodynamic forces associated with an increase in tubular fluid flow rate (TFFR). This increase in [Ca2+]i is proposed to be due to influx of extracellular Ca2+ through apical and basolateral mechanosensitive Ca2+ channels and release of Ca2+ from internal stores. We previously identified functional expression of the mechanosensitive Ca2+ channel PIEZO1 at the basolateral membranes of CCD principal (PC) and ICs (ASN Kidney Week, 2021). We hypothesize that PIEZO1 contributes to the flow-induced increase in [Ca2+]i necessary for BK channel-mediated FIKS.

Methods

To test this hypothesis, control and conditional IC-cell Piezo1 KO mice were fed a high K+ diet (HK, 5% K+) for 10 d. Isolated CCDs were microperfused in vitro to measure flow-induced increases in [Ca2+]i and net transepithelial transport (JX) of Na+ and K+ at slow and fast tubular fluid flow rates (0.9 and 5.5 nl/min.mm).

Results

Both PCs and ICs from control mice exhibited typical biphasic increases in [Ca2+]i in response to an acute increase in TFFR. However, flow-induced [Ca2+]i transients were significantly dampened in ICs from conditional IC-cell Piezo1 KO mice (p≤0.001, n=4/group). Similar rates (in pmol/min.mm) of flow-stimulated JNa were observed in CCDs from control (49.9±5.5) and KO (51.2±5.2, p=0.7; n=6, including 3 male and 3 female/group) mice with no significant differences between sex. FIKS, present in control CCDs (5.3±1.2), was absent in tubules from conditional KO mice (1.0±1.2; p<0.005). IC-cell Piezo1 KO male mice exhibited higher blood [K+] vs controls, 30 and 60 mins after gavage administration of 5% KCl solution (7.8±0.91 and 6.4±0.89 vs 6.5±0.35 and 5.1±0.17 mmol/L, n=6/group; p=0.01 and 0.02 respectively).

Conclusion

We conclude that mechanoactivated PIEZO1 channels mediate basolateral influx of Ca2+ in CCD ICs, and are indispensable for BK channel-mediated FIKS. We further speculate that basolateral PIEZO1 channels are activated by increases in membrane tension associated with an increase in TFFR.

Funding

  • NIDDK Support