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July 1, 2000British Journal of PharmacologyOpen Access

Sodium reabsorption in thick ascending limb of Henle's loop: effect of potassium channel blockade in vivo

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Population

Anaesthetized rats (nephrons with superficial glomeruli)

Comparison

Microperfusion of Henle's loop with K-free… vs Control conditions or K(+) supplementation

Design

Preclinical

Authors

DHDan HuangGuiyang College of Traditional Chinese MedicineHOHartmut OsswaldUniversity of TübingenVVVolker VallonNational Institutes of Health

Discussion

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Overview

Hypothesis-generating for K+ channel mediation of TAL Na+ reabsorption in rodents; leaves open translation to humans or selective blocker utility.

Key Points

  • To determine how pharmacological blockade of potassium channels affects fluid and sodium reabsorption in the thick ascending limb of Henle's loop in vivo.
  • Performed in vivo microperfusion downstream from late proximal tubule sites with potassium-free artificial tubular fluid in anesthetized rats with superficial glomeruli.
  • Tested the non-selective potassium channel blocker cesium (5–40 mM), selective channel blockers (charybdotoxin, glibenclamide, U37883A, verapamil, quinine), furosemide (100 µM), and luminal potassium supplementation.
  • Unselective potassium channel blockade with cesium (5–40 mM) dose-dependently increased early distal fluid delivery by up to ~20% and sodium delivery by up to ~185%.
  • Luminal potassium supplementation prevented sodium reabsorption inhibition caused by 15 mM cesium or intermediate conductance channel blockers (100 µM verapamil or quinine), but failed to prevent inhibition caused by 20 mM cesium.
  • Neither large-conductance (1 µM charybdotoxin) nor low-conductance (250 µM glibenclamide, 100 µM U37883A) potassium channel blockers altered loop of Henle fluid or sodium reabsorption.

Structured PICO

P
Population
Anaesthetized rats (nephrons with superficial glomeruli)
I
Intervention
Microperfusion of Henle's loop with K(+)-free artificial tubular fluid and K(+) channel blockers (Cs(+), charybdotoxin, glibenclamide, U37883A, verapamil, quinine)
C
Comparator
Control conditions or K(+) supplementation
O
Outcome
Early distal tubular delivery of fluid and Na(+) (Na(+) reabsorption)surrogate

Inhibition of K(+) channels in the thick ascending limb lowers luminal K(+) availability and transcellular Na(+) reabsorption, with more complete inhibition lowering paracellular Na(+) transport.

Cite This Study

Huang et al. (2000) studied this question.

synapsesocial.com/papers/6a92b2bcb1fb2e37bf1f666ahttps://doi.org/10.1038/sj.bjp.0703429
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Also Consider

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  1. 1Ionic channels in epithelial cell membranes1985 · 155 citations
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  3. 3Blocking agents of Ca2+-activated K+ channels in cultured medullary thick ascending limb cells1987 · 96 citations
  4. 4Two types of K+ channel in thick ascending limb of rat kidney1994 · 99 citations