Isovolumetric regulation of isolated S2 proximal tubules in anisotonic media.

Abstract

Sudden alteration in medium osmolality causes an osmometric change in proximal tubule cell size followed by restoration of cell volume toward normal in hypotonic but not in hypertonic medium. We determined the capability of isolated nonperfused proximal tubules to prevent a change in cell volume in anisotonic media. The external osmolality was gradually changed over a range from 110 to 480 mosM. At 1.5 mosM/min, cell volume remained constant between 167±9 and 361±7 mosM, a phenomenon termed isovolumetric regulation (IVR). Cells lost intracellular solutes in hypotonic and gained intracellular solutes in hypertonic media. Raffinose or choline chloride substitution showed that osmolality, rather than NaCG, signalled cell volume maintenance in hyperosmotic media. Cooling (7-100C) blocked IVR. IVR was maintained when osmolality was lowered at a rate of 27, but not at 42 mosM/min. IVR was not observed when the rate of osmolality increase exceeded 3 mosM/min. We conclude that proximal tubule cells sensitively regulate intracellular volume in an osmolality range of pathophysiologic interest by mechanisms dependent on (a) the rate of net water movement across basolateral membranes and (b) the absolute intracellular content of critical solutes.

Volume changes and whole cell membrane currents activated during gradual osmolarity decrease in C6 glioma cells: contribution of two types of K+ channels

“…According to the study of Lohr and Yohe (8) in C6 cells, swelling is prevented only when the osmolarity decrease is of 0.3-0.4 mosM/min and the osmolarity reductions do not exceed 20%. Therefore, C6 cells possess mechanisms to counteract hyposmotic swelling, which, however, appear less efficient than those present in renal cells, A6 cells, and some neurons, which are able to maintain constant volume in the face of osmolarity reductions similar to those used in the present study (7,21,24). This may be due to the contribution of amino acids and possibly other organic osmolytes, as discussed below.…”

“…The ubiquity of IVR as a mechanism of cell volume control has not been extensively explored. IVR has been described so far in two types of renal cells (6,7,22), in cerebellar granule neurons (21), and in a subset of hippocampal neurons (24). Other cell types such as C6 cells and cultured myocytes show IVR only over very short ranges of osmolarity and/or when the change in osmolarity is very small (8,18).…”

“…In most studies, however, cells are exposed to abrupt and large osmolarity reductions, which seldom occur in vivo, even in conditions of acute hyponatremia. An approach closer to the physiological situation is that devised by Lohr and Grantham (7), in which renal cells are exposed to small and gradual changes in external osmolarity. Under these conditions, cells are able to maintain a constant volume over a wide range of tonicities if the rate of change in osmolarity is Ͻ2.2 mosM/min.…”

“…This response was named "isovolumetric regulation" (IVR), a term reflecting the active nature of this process, because the unchanged volume seems not to be due to the absence of swelling but to a continuous volume adjustment accomplished by the efflux of intracellular osmolytes. This notion is based on the shrinkage observed in cells returned to an isosmotic medium, which, because of the decrease of intracellular osmolytes, is now hyperosmotic with respect to the intracellular medium (6,7). The ubiquity of IVR as a mechanism of cell volume control has not been extensively explored.…”

Energy turnover and the production of ammonium by the kidney: effect of hypernatremia

“…Fifth, it is possible that h e pH of the intracellular fluid of proximal cells was higher during hypernatremia. This might occur if there is a volume regulatory increase with alkaliraization in those cells that produce NH4' (Reid et al 1986), although most cells of the proximal tubule do not manifest a volume regulatory increase (Gagnon et al 1982;Linshaw et al 1957;Lohr and Grantham 1986).…”