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 a scending limb (TAL) is expected to lower Nai reabsorption through (i) reduc ing the luminal availability of K+ to reload the Na+-2Cl(-)-K+ cotransporte r and (ii) diminishing the lumen positive transepithelial potential differe nce which drives paracellular cation transport. 2 This issue was investigated in anaesthetized rats employing microperfusio n of Henle's loop downstream from late proximal tubular site with K+-free a rtificial tubular fluid in nephrons with superficial glomeruli. 3 The unselective K+ channel blocker Cs+ (5-40 mM) dose-dependently increas ed early distal tubular delivery of fluid and Na+ with a maximum increase o f similar to 20 and 185%, respectively, indicating predominant effects on w ater-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+ s upplementation. 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 flui d or Na+ reabsorption. 6 The intermediate conductance K+ channel blockers verapamil and quinine (1 00 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 obse rved 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 lum inal availability of K+ and thus transcellular Nar reabsorption in TAL. Mor e complete inhibition lowers paracellular Na+ transport probably by reducin g or even abolishing the lumen positive transepithelial potential differenc e. Under the latter conditions, transcellular Na+ transport may be restored by paracellular K+ backleak.