Ion channels on cytoplasmic membrane function to sense various environmental stimuli. We here determined the changes of genes encoding ion channels in Caenorhabditis elegans after exposure to polystyrene nanoparticles (PS-NPs). Exposure to 1-1000g/L PS-NPs could increase expressions of
egl-19,
mec-10,
trp-4,
trp-2,
tax-4,
cca-1,
unc-2, and
unc-93, and decrease the expressions of
cng-3,
mec-6,
ocr-2,
deg-1,
exc-4,
kvs-1, and
eat-2. Among these 15 ion channel genes, RNAi knockdown of
cng-3 or
eat-2 caused resistance to PS-NPs toxicity and RNAi knockdown of
egl-19,
cca-1,
tax-4, or
unc-93 induced susceptibility to PS-NPs toxicity, suggesting that
cng-3,
eat-2,
egl-19,
cca-1,
tax-4, and
unc-93 were involved in the control of PS-NPs toxicity. EGL-19 and CCA-1 functioned in intestinal cells to control PS-NPs toxicity, and CNG-3, EAT-2, EGL-19, TAX-4, and UNC-93 functioned in neuronal cells to control PS-NPs. Moreover, in intestinal cells of PS-NPs exposed worms,
cca-1 RNAi knockdown decreased
elt-2 expression, and
egl-19 RNAi knockdown decreased
daf-16 and
elt-2 expressions. In neuronal cells of PS-NPs exposed worms,
eat-2 RNAi knockdown increased
jnk-1,
mpk-1, and
dbl-1 expressions,
unc-93 RNAi knockdown decreased
mpk-1 and
daf-7 expressions, and
tax-4 RNAi knockdown decreased
jnk-1 and
daf-7 expressions. Therefore, two molecular networks mediated by ion channels in intestinal cells and neuronal cells were dysregulated by PS-NPs exposure in C.elegans. Our data suggested that the dysregulation in expressions of these ion channels mediated a protective response to PS-NPs in the range of g/L in worms.