CHARACTERIZATION OF VOLUME-ACTIVATED ION-TRANSPORT ACROSS EPITHELIAL MONOLAYERS OF HUMAN INTESTINAL T84 CELLS

The effects of hypo-osmolarity upon transepithelial ion transport in human intestinal cell layers have been investigated. Exposure of the basal-lateral surfaces to hypo-osmotic media resulted in a transient stimulation of inward short-circuit current (I(sc)). This transient stimulation of inward current by hypo-osmotic media was abolished by 100 mumol/l 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS). After prestimulation of inward I(sc) by vasoactive intestinal peptide (VIP) or by combinations of carbachol and prostaglandin E1, hypo-osmotic exposure of the basal-lateral surfaces resulted in a further transient stimulation of I(sc). The stimulation of I(sc) in these conditions was largely insensitive to DIDS inhibition. Exposure of the basal-lateral surfaces to hypo-osmotic media resulted in a stimulation of loop-diuretic-insensitive Rb-86 efflux across the basal-lateral surfaces. In addition, hypo-osmotic exposure of T84 cells is also associated with an increase in cytosolic Ca2+. It is concluded that the effects of hypo-osmotic exposure of T84 cells on secretory I(sc) are consistent with the activation of a DIDS-sensitive apical Cl- conductance and a basal-lateral K+ conductance. With prior activation of inward I(sc) by VIP via a cAMP-activated DIDS-insensitive apical Cl- conductance, augmentation of the secretory current by hypo-osmotic exposure is likely to result primarily from increased basal-lateral K+ current and loop-diuretic-sensitive Cl- uptake.