Characterisation 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 mol/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 hypoosmotic 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 ⁸⁶Rb 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.