Intercalated cell BKα subunit is required for flow-induced K+ secretion.
Rolando Carrisoza-Gaytan1, Evan C Ray2, Daniel Flores1
1Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
JCI Insight
|April 8, 2020
Summary
Intercalated cell BK channels are crucial for flow-induced potassium secretion in the kidney. Their absence impairs adaptation to high potassium diets, particularly in male mice.
Area of Science:
- Nephrology
- Physiology
- Molecular Biology
Background:
- BK channels in the kidney's cortical collecting duct (CCD) are implicated in potassium homeostasis.
- Their specific roles in intercalated cells (ICs) versus principal cells (PCs) remain unclear.
Purpose of the Study:
- To investigate the specific function of BK channels in ICs of the mammalian kidney.
- To determine the contribution of IC BK channels to flow-induced potassium secretion (FIKS) and potassium adaptation.
Main Methods:
- Generation of a mouse model with targeted disruption of the BK alpha subunit in ICs (IC-BKα-KO).
- Electrophysiological recordings of potassium currents in ICs.
- Metabolic studies involving high potassium diets and assessment of blood and urinary potassium levels.
- Microperfusion of CCDs to measure FIKS and epithelial sodium channel (ENaC)-mediated sodium absorption.
Main Results:
- Charybdotoxin-sensitive potassium currents were absent in ICs of IC-BKα-KO mice.
- IC-BKα-KO mice exhibited impaired adaptation to a high potassium diet, with significantly higher blood potassium in males.
- FIKS was abolished in IC-BKα-KO mice.
- Flow-stimulated ENaC-mediated sodium absorption was enhanced in female IC-BKα-KO mice.
Conclusions:
- BK channels in kidney ICs play a critical role in mediating FIKS.
- Sex influences the adaptive response to high potassium diets when IC BK channels are disrupted.
- These findings highlight the cell-specific functions of BK channels in renal potassium handling.
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