CHARACTERISTICS OF MEMBRANE-TRANSPORT PROCESSES OF MACULA DENSA CELLS

1. Macula densa (MD) cells are located within the thick ascending limb (TAL) and have their apical surface in contact with tubular fluid and their basilar region in contact with the glomerulus, These cells sens e changes in luminal fluid sodium chloride concentration ([NaCl]) and transmit signals resulting in changes in vascular resistance (tubulogl omerular feedback) and renin release. 2. Current efforts have focused on understanding the cellular transport mechanisms of MD cells. Progre ss in this area has benefited from the use of the isolated perfused TA L-glomerular preparation, which permits direct access to MD cells. 3. Using microelectrodes to measure basolateral membrane potential (V-BL) of MD cells, it was found that V-BL was very sensitive to changes in luminal fluid [NaCl]. As [NaCl] was elevated from 20 to 150 mmol/L, V- BL was found to depolarize by over 30 mV. 4. Basolateral membrane pote ntial measurements were also used to identify an apical Na+:2Cl(-):Kcotransport pathway in MD cells that is the major pathway for NaCl ent ry into these cells. 5. Other work identified a basolateral chloride c hannel that is presumed to be responsible for changes in V-BL during a lterations in luminal [NaCl]. This channel, which is the predominant c onductance across the basolateral membrane, may be regulated by intrac ellular Ca2+ and cAMP. 6. An apical Na+:H+ exchanger in MD cells was d etected by measuring changes in intracellular pH using the fluorescent probe 2',7'-bis-(2-carboxyethyl)-5(and-6) carboxyfluorescein. 7. Usin g patch-clamp techniques, a high density of pH- and Ca2+-sensitive Kchannels was observed at the apical membrane of MD cells. 8. Other stu dies found that, at the normal physiological conditions prevailing at the end of the TAL (luminal [NaCl] of 20-60 mmol/L), reabsorption medi ated by MD cells is very sensitive to changes in luminal [NaCl].