Recent studies have suggested that octopamine (OA) and dopamine (DA) play important roles in mediating the reward and punishment signals, respectively, in olfactory learning in insect. However, their target molecules and the signaling mechanisms are not fully understood. In this study, we showed for the first time that OA and DA modulate the Na+-activated K+ (KNa) channels in an opposite way in Kenyon cells isolated from the mushroom body of the cricket, Gryllus bimaculatus. Patch-clamp recordings showed that the single-channel conductance of the KNa channel was about 122 pS with high K+ in the patch pipettes. The channel was found to be activated by intracellular Na+ but less activated by Li+. K+ channel blockers TEA and quinidine reduced the open probability (Po) of this channel. Bath application of OA and DA respectively increased and decreased the Po of KNa channel currents. An increase and a decrease in Po of KNa channels were also observed by applying the membrane-permeable analogs 8-Br-cyclic-AMP and 8-Br-cGMP, respectively. Furthermore, it was revealed that cAMP-induced increase and cGMP-induced decrease in Po were attenuated by the specific protein kinase A (PKA) inhibitor H-89 and protein kinase G (PKG) inhibitor KT5823, respectively. These results indicate that the KNa channel is a target molecule for OA and DA and that cAMP/PKA and cGMP/PKG signaling pathways are also involved in the modulation of KNa channels.