Characteristics of membrane transport processes of macula densa cells

Abstract

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 sense changes in luminal fluid sodium chloride concentration ([NaCl]) and transmit signals resulting in changes in vascular resistance (tubuloglomerular feedback) and renin release. 2. Current efforts have focused on understanding the cellular transport mechanisms of MD cells. Progress in this area has benefited from the use of the isolated perfused TAL-glomerular preparation, which permits direct access to MD cells. 3. Using microelectrodes to measure basolateral membrane potential (VBL) of MD cells, it was found that VBL was very sensitive to changes in luminal fluid [NaCl]. As [NaCl] was elevated from 20 to 150 mmol/L, VBL was found to depolarize by over 30 mV. 4. Basolateral membrane potential measurements were also used to identify an apical Na+:2Cl-:K+ cotransport pathway in MD cells that is the major pathway for NaCl entry into these cells. 5. Other work identified a basolateral chloride channel that is presumed to be responsible for changes in VBL during alterations in luminal [NaCl]. This channel, which is the predominant conductance across the basolateral membrane, may be regulated by intracellular Ca2+ and cAMP. 6. An apical Na+:H+ exchanger in MD cells was detected by measuring changes in intracellular pH using the fluorescent probe 2',7'-bis-(2-carboxyethyl)-5(and-6) carboxyfluorescein. 7. Using patch-clamp techniques, a high density of pH- and Ca(2+)-sensitive K+ channels was observed at the apical membrane of MD cells. 8. Other studies found that, at the normal physiological conditions prevailing at the end of the TAL (luminal [NaCl] of 20-60 mmol/L), reabsorption mediated by MD cells is very sensitive to changes in luminal [NaCl].