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GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
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The thick ascending limb of the nephron loop has Na+–K+–2Cl− symporters in the apical membranes of its cells. These symporters simultaneously reclaim one sodium ion, one potassium ion, and two chloride ions from the tubular fluid. Sodium ions are actively transported into the interstitial fluid at the base and sides of the cell, diffusing into the vasa recta. Chloride ions move through leakage channels in the basolateral membrane into the interstitial fluid and then into the...
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The early phase of the DCT manages the reabsorption of approximately 10-15% of filtered water, 5–10% of filtered sodium, and 5–10% of filtered chloride. This process is facilitated by Na+–Cl− symporters in apical membranes and sodium-potassium pumps, as well as Cl− leakage channels in basolateral membranes. The early DCT also stands out as a site where parathyroid hormone (PTH) stimulates calcium reabsorption, depending on the body's requirements.
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Related Experiment Video

Updated: Dec 24, 2025

Measurement of Ion Concentration in the Unstirred Boundary Layer with Open Patch-Clamp Pipette: Implications in Control of Ion Channels by Fluid Flow
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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
PubMed
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.

Keywords:
Cell BiologyEpithelial transport of ions and waterIon channelsMouse modelsNephrology

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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.