A side effect of CBZ in therapy is hyponatremia, however, it remained unclear which targets are responsible for these side effects. In Ussing chamber experiments we showed that Clsecretion in rat distal colon was inhibited by CBZ. To identify the respective target we expressed the key mediators of colonic Clsecretion in Xenopus laevis oocytes and tested for the effects of CBZ in two electrode voltage clamp experiments. Conductances were measured at -80mV, 0mV and +30mV clamp voltage. Time constants of voltage activation at 0mV clamp voltage and halfmaximal activation voltage from tail currents at -30mV clamp voltage were determined, as appropriate. Neither CFTR nor KCNQ1 were inhibited by CBZ. In contrast KCNQ1 was activated by CBZ if coexpressed with KCNE3 or KCNE1. CBZ increased the conductance of KCNQ1/KCNE1 by 34±12% (n=9) and of KCNQ1/KCNE3 by 30±11% (n=15). The time constant of activation was accelerated in KCNQ1/KCNE3 from 101±8ms to 88±6ms by CBZ. All effects were reversible. Taken together inhibition of cAMP mediated Cl^-secretion by CBZ is not mediated via direct channel interaction. CBZ is shown to activate KCNQ1 if coexpressed with its subunits KCNE1 or KCNE3. Further investigations on neuronal K⁺ channels of the KCNQ family with relevance for epilepsy might open a new field for the understanding of antiepileptic CBZ action.