Block of Kir channels by flonicamid disrupts salivary and renal excretion of insect pests

Flonicamid is a selective insecticide for the control of sap-sucking insects; it exerts toxic effects by inhibiting insect feeding. However, its molecular target remains elusive. In this study, we functionally characterized NlKir1 channels of the brown planthopper (Nilaparvata lugens) in HEK293 cells. Homomeric NlKir1 channels generated inward-rectifying K+ currents. Flonicamid inhibited NlKir1 channels at nanomolar concentrations. Furthermore, flonicamid inhibited honeydew and salivary secretions of planthoppers, and reduced the renal excretion of female mosquitoes in a dose-dependent manner. The inhibitory effect of flonicamid on fluid secretion of isolated Malpighian tubules from Culex pipiens pullens was comparable to that of the selective Kir1 inhibitor. The observed physiological alterations by flonicamid are likely mediated by Kir1 channels and could lead to the disruption of feeding behaviors and eventually lethality. Our study establishes the Kir1 channel as the target of flonicamid and provided new insights into the mode of action of flonicamid.