Nystatin and valinomycin induce tubuloglomerular feedback

F1102–F1108, 2001. First published September 21, 2001; 10.1152/ajprenal.00357.2001.—The macula densa expresses a luminal Na1-K1-2Cl2 cotransporter and a basolateral Cl2 conductance. Although it is known that cotransport of Na1, K1, and Cl2 is the first step in tubuloglomerular feedback (TGF), subsequent steps are unclear. We hypothesized that Na1-K1-2Cl2 entry via the luminal Na1-K1-2Cl2 cotrans-porter elevates intracellular Cl2, increases electrogenic Cl2 efflux across the basolateral membrane, and depolarizes the macula densa, initiating TGF. We perfused afferent arte-rioles with macula densa attached. The macula densa was perfused with solutions containing either 5 mM Na1 and 3 mM Cl2 (low NaCl) or 80 mM Na1 and 77 mM Cl2 (high NaCl). When the macula densa perfusate was changed from low to high NaCl, afferent arteriole diameter decreased fro