Regulation of renal tubule cell volume in hypotonic media

Renal tubule cell volume is thought to be kept constant by a cation pump. When active transport is blocked, intracellular impermeant solutes cause cells to swell. Cell size is then determined by transmembrane hydrostatic and colloid osmotic forces. We studied the importance of passive transmembrane forces in determining cell size in isolated rabbit proximal straight tubules (PST). We blocked active solute transport with ouabain and evaluated subsequent changes in cell size by measuring outer diameter of nonperfused tubules. Tubules in a ouabain and 6 g/100 ml protein bath swelled only 40% above control. However, removal of the tubule basement membrane with collagenase dissipated a transmembrane hydrostatic pressure and caused more swelling. Final cell volume was determined largely by bath protein concentration. Tubules in ouabain and collagenase swelled enormously in hyponcotic protein, moderately in isoncotic protein, and could be shrunk below control in hyperoncotic protein. Intracellular colloid osmotic pressure was estimated to exceed 38 cmH20. We conclude that hydrostatic and colloid osmotic forces are major determinants of cell size in isolated PST treated with ouabain.

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Effect of metabolic inhibitors on renal tubule cell volume

AJP Renal Physiology ◽

10.1152/ajprenal.1980.239.6.f571 ◽

1980 ◽

Vol 239 (6) ◽

pp. F571-F577 ◽

Cited By ~ 1

Author(s):

M. A. Linshaw

Keyword(s):

Cell Volume ◽

Cell Size ◽

Renal Tubule ◽

Cation Transport ◽

Metabolic Inhibitors ◽

Cell Swelling ◽

Tubule Cell ◽

Bathing Medium ◽

Cation Pump ◽

Renal Tubule Cell

Renal tubule cell volume is thought to be kept constant by a cation pump. Ouabain, by inhibiting Na+-K+-ATPase, blocks cation transport with resultant cell swelling, but the degree of swelling is less than expected were active cation transport completely inhibited. Although the relatively rigid tubule basement membrane may limit swelling of ouabain-treated tubules, some investigators have alternatively postulated that an energy-dependent ouabain-insensitive cation pump regulates cell size. This notion derives from studies of renal cortical slices in which metabolic inhibitors such as 2,4-dinitrophenol (DNP) cause more swelling than ouabain. We blocked cellular metabolism of isolated rabbit proximal straight tubules by adding metabolic inhibitors to or removing acetate and glucose (energy substrate) from the bathing medium and evaluated subsequent changes in cell size by measuring outer diameter of nonperfused tubules. In isotonic medium, cell volume increased 36% with addition of 10(-4) M ouabain, 40% with 10(-2) M DNP, 46% with 10(-3) M cyanide, 39% with ouabain + DNP + cyanide, and 37% with removal of bath substrate (P = NS). We conclude that renal tubule cell volume is not regulated by a unique-ouabain-insensitive cation pump.

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Effect of ouabain and colloid osmotic pressure on renal tubule cell volume

AJP Renal Physiology ◽

10.1152/ajprenal.1978.235.5.f480 ◽

1978 ◽

Vol 235 (5) ◽

pp. F480-F491

Author(s):

M. A. Linshaw ◽

F. B. Stapleton

Keyword(s):

Osmotic Pressure ◽

Cell Volume ◽

Renal Tubule ◽

Colloid Osmotic Pressure ◽

Cell Swelling ◽

Outer Diameter ◽

Tubule Cell ◽

Fluid Flux ◽

Renal Tubule Cell ◽

Collecting Tubules

Proximal renal tubule cell volume increases in ouabain but cell swelling is limited by the tubule basement membrane (TBM) and the colloid osmotic pressure from the bath protein. We compared the effect of ouabain, external protein concentration, and TBM on cell volume of proximal convoluted (PCT), proximal straight (PST), and cortical collecting tubules (CCT). We blocked active solute transport with ouabain and evaluated cell size by measuring the outer diameter of nonperfused tubules. Proximal tubules in ouabain swelled 35–40% in isoncotic medium and 20–25% further in hyponcotic medium (0.3 g/100 ml albumin), but PCT swelled faster than PST. The CCT swelled minimally in similar mediums, indicating pronounced heterogeneity in the response of cortical nephron segments to ouabain. In the presence of ouabain, all tubules swelled extensively when we removed the TBM with collagenase. In the hyponcotic medium fluid flux across the peritubular membrane was 0.081, 0.049, and 0.030 nl/min per mm tubule length for PCT, PST, and CCT, respectively. The rates of fluid flux in PCT and PST were proportional to estimates of the respective basolateral surface areas. We suggest that differences in swelling rates between proximal segments reflect variations in surface area rather than intrinsic peritubular membrane permeability to solute and water.

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