Ionic transport in macula densa cells. Recent work has provided substantial insights into functional characteristics of macula densa (MD) cells. Microelectrode and patch-clamp experiments on the rabbit isolated thick ascending limb (TAL)/glomerulus preparation have shown that MD cells possess a furosemide-sensitive Na:K:2Cl cotransporter, an apical 41-pS K+ channel, and a dominant basolateral Cl- conductance. Increasing luminal fluid [NaCl] ([NaCl](L)) results in furosemide-sensitive cell depolarization due to a rise in intracellular [Cl-] that stimulates basolateral electrogenic Cl- efflux. Intracellular pH (pH(i)) measurements show the presence of an apical Na:H exchanger that couples transepithelial Na+ transport to pH(i). Experimental results and thermodynamic considerations allow estimation of intracellular [Na+] and [Cl-] ([Na+](i), [Cl-](i)) under different conditions. When the Na:K:2Cl cotransporter is equilibrated (or in the presence of furosemide), [Na+](i) and [Cl-](i) are low (~6 to 7 mM), whereas when the cotransporter is fully activated, [Na+](i) and [Cl- ](i) increase substantially to approximately 70 and 20 mM, respectively. Finally, luminal addition of NH4+ produces cell acidification that depends on NH4+ apical transport rate through the Na:K:2Cl. Using a simple transport model for NH4+, the initial NH4+ influx rate in MD cells is comparable to the corresponding flux in TAL. This challenges the idea that MD cells have a low transport activity but supports our findings about large changes in intracellular concentrations as a function of [NaCl](L).