The effect of short-chain fatty acids on Cl- and K+ conductance in rat colonic crypts

The effect of butyrate on membrane potential and membrane currents of colonic enterocytes was studied with the whole-cell patch-clamp method. Superfusion of crypts from the rat distal colon with butyrate-containing solutions induced a membrane depolarization of 16.5 +/- 2.3 mV. This response was only observed in the upper third of the crypt. The depolarization was dependent on the presence of Cl- and was accompanied by an increase in membrane inward current, indicating that it is caused by an increase in Cl- conductance. Membrane outward current, however, behaved inconsistently. Whereas in most cells an increase was observed, about 25% of the cells responded with a decrease. This unexpected inhibition of the outward current probably represents a decrease of K+ conductance caused by the cellular acidification in the presence of butyrate. Manoeuvres carried out to acidify the cell interior, like perfusion with acid buffer solutions or inhibition of the Na+/H+ exchanger by amiloride, mimicked this inhibition of the K+ conductance. Orientating cell-attached patch-clamp recordings performed in parallel revealed an activation of previously silent basolateral Cl- channels by butyrate. They had a linear current/voltage relationship and a single-channel conductance of 20-30 pS. The butyrate-induced depolarization was not dependent on intracellular adenosine 5'-triphosphate (ATP) and was also observed when the buffer capacity of the pipette for Ca2+ was increased. It was also not inhibited by guanosine-5'-O(2-thiodiphosphate) (GDP[beta S]).(ABSTRACT TRUNCATED AT 250 WORDS)