Regulation of sorbitol efflux in different renal medullary cells: Similarities and diversities

It is well accepted that organic osmolytes, including sorbitol, play a majo r role in the volume regulation of renal medullary cells. The signal leadin g to an activation of release channels during RVD is, however, poorly under stood. Hypotonicity induced sorbitol efflux was investigated in freshly iso lated rat inner medullary collecting duct (IMCD) cells and in rabbit medull ary thick ascending limb of Henle's loop (TALH) cells biochemically or usin g labeled sorbitol. The time course of release was compared with changes in cell volume, measured by confocal microscopy, and alterations in cell calc ium (Ca-i) determined by Fura 2 technology. In IMCD cells sorbitol release, volume decrease and Ca-i transients show a close temporal correlation. In addition increases in Ca-i without volume changes stimulate sorbitol efflux . In TALH cells sorbitol release starts after a significant lag time and re aches a maximum when cell volume is already partially restored. The same di screpancy is observed with regard to changes in Ca-i and sorbitol efflux. T hese studies suggest that in IMCD cells changes in Ca-i are the main regula tor for the sorbitol permeability of the plasma membrane. The sorbitol chan nel present in TALH cells seems to operate predominantly independently of C a-i. Despite this diversity in signal transduction the sorbitol channels in both renal cell types appear, however, not to be stretch-activated. Copyri ght (C) 2000 S. Karger AG Basel.