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• W2065978737 abstract "Based on previous in vitro studies, inhibition of K+ recycling in thick ascending limb (TAL) is expected to lower Na+ reabsorption through (i) reducing the luminal availability of K+ to reload the Na+-2Cl−-K+ cotransporter and (ii) diminishing the lumen positive transepithelial potential difference which drives paracellular cation transport. This issue was investigated in anaesthetized rats employing microperfusion of Henle's loop downstream from late proximal tubular site with K+-free artificial tubular fluid in nephrons with superficial glomeruli. The unselective K+ channel blocker Cs+ (5–40 mM) dose-dependently increased early distal tubular delivery of fluid and Na+ with a maximum increase of ∼20 and 185%, respectively, indicating predominant effects on water-impermeable TAL. The modest inhibition of Na+ reabsorption in response to the 15 mM of Cs+ but not the enhanced inhibition by 20 mM Cs+ was prevented by luminal K+ supplementation. Furthermore, pretreatment with 20 mM Cs+ did not attenuate the inhibitory effect of furosemide (100 μM) on Na+-2Cl−-K+ cotransport. Neither inhibitors of large (charybdotoxin 1 μM) nor low (glibenclamide 250 μM; U37883A 100 μM) conductance K+ channels altered loop of Henle fluid or Na+ reabsorption. The intermediate conductance K+ channel blockers verapamil and quinine (100 μM) modestly increased early distal tubular Na+ but not fluid delivery, indicating a role for this K+ channel in Na+ reabsorption in TAL. As observed for equieffective concentrations of Cs+ (15 mM), Na+ reabsorption was preserved by K+ supplementation. The results indicate that modest inhibition of K+ channels lowers the luminal availability of K+ and thus transcellular Na+ reabsorption in TAL. More complete inhibition lowers paracellular Na+ transport probably by reducing or even abolishing the lumen positive transepithelial potential difference. Under the latter conditions, transcellular Na+ transport may be restored by paracellular K+ backleak. British Journal of Pharmacology (2000) 130, 1255–1262; doi:10.1038/sj.bjp.0703429" @default.
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• W2065978737 date "2000-07-01" @default.
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• W2065978737 title "Sodium reabsorption in thick ascending limb of Henle's loop: effect of potassium channel blockade<i>in vivo</i>" @default.
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• W2065978737 doi "https://doi.org/10.1038/sj.bjp.0703429" @default.
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