Activation of Ca2+- and cAMP-sensitive K+ channels in murine colonic epithelia by 1-ethyl-2-benzimidazolone

1-Ethyl-2-benzimidazolone (EBIO) caused a sustained increase inelectrogenic Cl secretionin isolated mouse colon mucosae, an effect reduced by blockingbasolateral K⁺ channels. TheCa²⁺-sensitiveK⁺ channel blocker charybdotoxin(ChTX) and the cAMP-sensitive K⁺channel blocker 293B were more effective when the other had been addedfirst, suggesting that both types ofK⁺ channel were activated. EBIOdid not cause Cl secretionin cystic fibrosis (CF) colonic epithelia. In apically permeabilizedcolonic mucosae, EBIO increased theK⁺ current when a concentrationgradient was imposed, an effect that was completely sensitive toChTX. No current sensitive to trans-6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane (293B) was found in this condition. However, the presence ofbasolateral cAMP-sensitive K⁺channels was demonstrated by the development of a 293B-sensitive K⁺ current after cAMP applicationin permeabilized mucosae. In isolated colonic crypts EBIO increasedcAMP content but had no effect on intracellularCa²⁺. It is concludedthat EBIO stimulates Clsecretion by activatingCa²⁺-sensitive and cAMP-sensitiveK⁺ channels, therebyhyperpolarizing the apical membrane, which increases the electricalgradient for Cl effluxthrough the CF transmembrane conductance regulator (CFTR). CFTR is alsoactivated by the accumulation of cAMP as well as by direct activation.