Effects of short-chain fatty acids on cell volume regulation and chloride transport in the distal colon

Superfusion of isolated crypts from rat colon with sodium butyrate-containing solutions induced an amiloride-sensitive swelling of the cells at the upper one third of the crypt. In HCO3- containing buffer, swelling was followed by regulatory volume decrease, which was inhibited by K+ and C- channel blockers and inhibitors of leukotriene synthesis. Whole cell patch clamp recordings revealed that butyrate induced a membrane depolarization, which was dependent on Cl- and was accompanied by an increase in membrane inward current, indicating an increase in Cl- conductance. Membrane outward (K+) current, however, behaved inconsistently, suggesting an activation of swelling induced K+ currents, but an inhibition of pH-sensitive K+ currents due to the cellular acidification. Cell-attached patch-clamp recordings showed an activation of basolateral Cl- channels by butyrate. The lipoxygenase inhibitor, NDGA (nordihydroguaiaretic acid), inhibited the butyrate response and even reversed it into a slight hyperpolarization indicating that the butyrate-induced Cl- channels, but not the K+ channels, are stimulated by a leukotriene. Short-chain fatty acids concentration-dependently decreased short-circuit current (Isc). The decrease in Isc was diminished by a Cl- channel blocker, NPPB (5-nitro-2-[3-phenylpropylamino]-benzoate), and a lipoxygenase inhibitor, NDGA. Butyrate stimulated the mucosa to serosa fluxes (Jms) of Na+ and Cl-. The effect on J(ms)(Cl) was blocked by NPPB or NDGA. The stimulation of J(ms)(Cl) correlated with the degree of metabolism of the short chain fatty acid. Consequently, two factors seem to be responsible for the stimulation of Cl- absorption by short-chain fatty acids: (a) the intracellular production of HCO3- during the oxidation of short-chain fatty acids as substrate for the apical Cl-/HCO3- exchanger, and (b) the activation of volume-sensitive basolateral Cl- channels. (C) 1997 Elsevier Science Inc.