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

1 Based on previous in vitro studies, inhibition of K+ recycling in thick ascending limb (TAL) is expected to lower Nai 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. 2 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. 3 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 similar to 20 and 185%, respectively, indicating predominant effects on water-impermeable TAL. 4 The modest inhibition of Naf 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 mu M) on Na+-2Cl(-)-K+ cotransport. 5 Neither inhibitors of large (charybdotoxin 1 mu M) nor low (glibenclamide mu M; U37883A 100 mu M) conductance K+ channels altered loop of Henle fluid or Na+ reabsorption. 6 The intermediate conductance K+ channel blockers verapamil and quinine (100 mu M) modestly increased early distal tubular Na+ but not fluid delivery, indicating a role for this KI channel in Na+ reabsorption in TAL. As observed for equieffective concentrations of Csi (15 mM), Na+ reabsorption was preserved by K+ supplementation. 7 The results indicate that modest inhibition of K+ channels lowers the luminal availability of K+ and thus transcellular Nar 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.