Involvement of butyrate in electrogenic K⁺ secretion in rat rectal colon

Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are synthesized from dietary carbohydrates by colonic bacterial fermentation. These SCFAs supply energy, suppress cancer, and affect ion transport. However, their roles in ion transport and regulation in the intracellular environment remain unknown. In order to elucidate the roles of SCFAs, we measured short-circuit currents (I_SC) and performed RT-PCR and immunohistochemical analyses of ion transporters in rat rectal colon. The application of 30 mM butyrate shifted I_SC in a negative direction, but did not attenuate the activity of epithelial Na⁺ channels (ENaC). The application of bumetanide, a Na⁺-K⁺-2Cl^- cotransporter inhibitor, to the basolateral side reduced the negative I_SC shift induced by butyrate. The application of XE991, a KCNQ-type K⁺ channel inhibitor, to the apical side decreased the I_SC shift induced by butyrate in a dose-dependent manner. The I_SC shift was independent of HCO₃^- and insensitive to ibuprofen, an SMCT1 inhibitor. The mucosa from rat rectal colon expressed mRNAs of H⁺-coupled monocarboxylate transporters (MCT1, MCT4, and MCT5, also referred to as SLC16A1, SLC16A3, and SLC16A4, respectively). RT-PCR and immunofluorescence analyses demonstrated that KCNQ2 and KCNQ4 localized to the apical membrane of surface cells in rat rectal colon. These results indicate that butyrate, which may be transported by H⁺-coupled monocarboxylate transporters, activates K⁺ secretion through KCNQ-type K⁺ channels on the apical membrane in rat rectal colon. KCNQ-type K⁺ channels may play a role in intestinal secretion and defense mechanisms in the gastrointestinal tract.