UCLA

Pesticides have been extensively used in agriculture for over a century but concerns regarding their negative impact on human health persist. The relationship between pesticides and human pathogenesis is complex and poorly understood, with myriad factors influencing their effects. Among the health risks associated with pesticide exposure, the development of neurodegenerative diseases, including Parkinson's disease (PD), is of particular concern. The fungicide Ziram has been shown to cause neurotoxicity as well as an increased risk of PD in those who have been chronically exposed. However, the precise mechanism for this effect remains unclear. In the fruitfly Drosophila melanogaster, Ziram has been shown to increase neuronal excitability by blocking the ether-a-gogo (eag) family of potassium channels. Ziram also increases excitability in mammalian neurons, and we here test the hypothesis that Ziram directly blocks hERG (human eag related gene) potassium channels. Using a non-neuronal cell line expressing hERG we find that Ziram indeed does block this potassium channel. Our data suggest that Ziram acts directly on hERG rather than an accessory subunit.