Recent work has provided substantial insights into functional characte
ristics of macula densa (MD) cells. Microelectrode and patch-clamp exp
eriments 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 basol
ateral Cl- conductance. Increasing luminal fluid [NaCl] ([NaCl](L)) re
sults in furosemide-sensitive cell depolarization due to a rise in int
racellular [Cl-] that stimulates basolateral electrogenic Cl- efflux.
Intracellular pH (pH(i)) measurements show the presence of an apical N
a:H exchanger that couples transepithelial Na+ transport to pH(i). Exp
erimental results and thermodynamic considerations allow estimation of
intracellular [Na+] and [Cl-] ([Na+](i), [Cl-](i)) under different co
nditions. When the Na:K:2Cl cotransporter is equilibrated (or in the p
resence of furosemide), [Na+](i) and [Cl-](i) are low (similar to 6 to
7 mM); whereas when the cotransporter is fully activated, [Na+](i) an
d [Cl-](i) increase substantially to approximately 70 and 20 mM, respe
ctively. Finally, luminal addition of NH4+ produces cell acidification
that depends on NH4+ apical transport rate through the Na:K:2Cl. Usin
g a simple transport model for NH4+, the initial NH4+ influx rate in M
D cells is comparable to the corresponding Aux 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 fun
ction of [NaCl](L).