Fig. 3. Models of transepithelial NaCl and KCl secretion in Malpighian tubules of Aedes aegypti. The cations Na⁺ and K⁺ take a transcellular pathway and Cl^– takes a paracellular shunt pathway. Transcellular and paracellular pathways are electrically coupled, forming an intraepithelial current loop. The current generator is the V-type H⁺-ATPase located in the apical membrane of principal cells (Beyenbach, 2001). Current across the apical membrane is carried by H⁺. Current returning to the cytoplasmic face of the V-type H⁺-ATPase is carried by Cl^– ions passing from the hemolymph to the tubule lumen through the paracellular pathway, by K⁺ and Na⁺ entering the cell across the basolateral membrane and by Cl^– leaving the cell through Cl^– channels (Yu et al., 2003). Barium blocks basolateral membrane K⁺ channels, thereby increasing the resistance of the basolateral membrane (R_bl) and decreasing the loop current. The net effect is the inhibition of transepithelial NaCl, KCl and fluid secretion. Bumetanide blocks Na⁺/K⁺/2Cl^– cotransport across the basolateral membrane, leaving electroconductive pathways largely intact. As a result, intraepithelial current flow is not affected and rates of transepithelial cation, anion and fluid secretion remain unchanged. However, rates of transepithelial K⁺ secretion decrease and Na⁺ secretion increase because one major pathway for K⁺ entry is blocked, leaving three other Na⁺ entry pathways open. V_s, rate of fluid secretion; E, electromotive force; V, voltage; R, resistance; a, apical membrane; bl, basolateral membrane; sh, epithelial shunt; t, transepithelial.