Effect of various diuretics on membrane voltage of macula densa cells. Whole-cell patch-clamp experiments.
The tubuloglomerular feedback mechanism is inhibited by diuretics such as furosemide. For the macula densa (MD) cells similar transport systems, as present in thick ascending limb (TAL) cells, have been suggested. To examine this further, membrane voltages (Vm) of MD cells were recorded with the fast or slow whole-cell patch-clamp method. The effects of diuretics on voltages and the conductance properties of these cells were examined. Vm of MD cells measured with the whole-cell patch-clamp method were as high as those in TAL cells: -72 +/- 1 mV (n = 21). An increase in the extracellular K+ concentration by 15 mmol/l depolarized Vm of MD cells by 11 +/- 1 mV (n = 18). Ba2+ (1 mmol/l) reversibly depolarized MD cells by 10 +/- 2 mV (n = 10). Thus, MD cells possess a K+ conductance that could allow for the recycling of K+ taken up by the Na(+)-2 Cl(-)-K+ cotransporter. MD cells hyperpolarized reversibly upon addition of the loop diuretics furosemide, piretanide and torasemide, whereas muzolimine and hydrochlorothiazide, neither one acting on this cotransport system in other preparations including the TAL, had no effect on Vm. MD cells most likely possess the same cotransport system as the TAL cells, which drives NaCl reabsorption in the TAL and serves as sensor for the tubular NaCl concentration in MD cells.
Physiologisches Institut, Albert-Ludwigs-Universität Freiburg, Germany.
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Schlatter
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D018118:Chloride Channels; D004232:Diuretics / Q000494:pharmacology*; D004553:Electric Conductivity; D004594:Electrophysiology; D005665:Furosemide / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000648:ultrastructure*; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000502:physiology; D009156:Muzolimine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D000077786:Torsemide
D018118:Chloride Channels; D004232:Diuretics; D008565:Membrane Proteins; D015221:Potassium Channels; D013449:Sulfonamides; D009156:Muzolimine; D006852:Hydrochlorothiazide; D001464:Barium; D005665:Furosemide; C015451:piretanide; D011188:Potassium; D000077786:Torsemide