Role of Ca2+ in sorbitol release from rat inner medullary collecting duct (IMCD) cells under hypoosmotic stress

The role of Ca2+ was studied in the release of the organic osmolyte sorbitol from rat IMCD cells in response to hypoosmotic stress. When cells were exposed to hypoosmotic media, sorbitol release was greatly reduced in Ca-free media which, on readmission of Ca2+, returned to control values. Under isoosmotic conditions, the ionophore A23187 stimulated sorbitol release without any effect on cell volume. Addition of trifluoperazine, a calmodulin inhibitor, but not the protein kinase C inhibitor H-7, inhibited the osmotically-activated sorbitol release. These results suggest that sorbitol release is a calmodulin-dependent event, possibly activated by a rise in intracellular calcium as a result of cell swelling.