Chlorantraniliprole affects ion channels in Helicoverpa armigera

The chlorantraniliprole , an insecticide called diamide used to control lepidopteran pests, altered sodium and potassium channels in neurons of Helicoverpa armigera larvae. The information is contained in a scientific study, which also identified glial cell responses in the ventral nerve cord of larvae after exposure to the insecticide.

The research evaluated the neurotoxicity of chlorantraniliprole in third-instar larvae of Helicoverpa armigera. Scientists combined whole-cell patch-clamp electrophysiology, single-cell RNA sequencing, and RT-qPCR. This approach allowed them to observe effects on neuronal ion channels and map cell types in the ventral nerve cord.

Insecticide action

Chlorantraniliprole acts on ryanodine receptors. This action causes uncontrolled calcium release in insects and leads to muscle paralysis. The new study indicates another component in the toxic effect. At relatively high concentrations, the insecticide modulated voltage-gated sodium channels and reduced voltage-gated potassium channel currents.

Sodium channels

In sodium channels, chlorantraniliprole shifted activation and inactivation curves to more negative potentials. The product also delayed channel recovery after inactivation. According to the data, the recovery time increased from 0,24474 milliseconds in the control group to 1,01362 milliseconds with 100 micromolar of chlorantraniliprole. This value is approximately 4,14 times that of the control.

Electrophysiological recordings also showed a reduction in the peak amplitude of the sodium current with increasing insecticide concentration. Channel activation occurred at more negative potentials after treatment. In the control group, sodium channels activated between -40 and -30 millivolts. With 100 micromolar of chlorantraniliprole, activation occurred near -80 millivolts.

Potassium channels

In potassium channels, the insecticide did not noticeably alter the activation properties. However, it reduced the peak current in a dose-dependent pattern. This effect may impair neuronal repolarization. The combination of altered sodium channels and inhibition of potassium current may compromise the electrical balance of neurons.

The researchers also constructed the first single-cell transcriptomic atlas of the ventral nerve cord of larvae of Helicoverpa armigera. The sequencing analyzed 10.823 high-quality cells, with an average of 1.494 genes detected per cell. After normalization and dimensionality reduction, the cells formed 18 clusters.

Cell phone note

Cellular annotation indicated neuronal and non-neuronal populations. Among neurons, the study identified markers associated with cholinergic, glutamatergic, and GABAergic systems. Among glial cells, scientists recognized perineurial glia, subperineurial glia, astrocytes, and enveloping glia. Tracheal cells, neuroblasts, and clusters without definitive annotation also appeared.

Analysis of glial cells highlighted two genes: NKCC and UGT39B1. NKCC showed predominant expression in perineurial glia. UGT39B1 appeared enriched in subperineurial glia. After exposure to chlorantraniliprole at a lethal concentration of 30 for 24 hours, both genes showed a significant increase in expression in nervous tissue.

UGT39B1 belongs to the UDP-glycosyltransferase family. These enzymes participate in the conjugation of exogenous substances and can act in metabolic elimination. The elevation of UGT39B1 after treatment suggests a response linked to detoxification. NKCC encodes a sodium, potassium, and chloride cotransporter. Its high expression may reflect an adjustment in the ionic homeostasis of glial cells after chemical stress.

Neurotoxic action

The data support a proposed neurotoxic mechanism with two components. The first involves neuronal targets, with modulation of sodium channels and reduction of potassium currents. The second involves glial cells, with a response from genes associated with ion transport and metabolism. Scientists describe this combination as a dual-target mechanism, involving neurons and glia.

The work also indicates possible avenues for resistance management. The identification of NKCC and UGT39B1 as genes responsive to chlorantraniliprole offers candidates for studies on synergists and on strategies aimed at delaying the evolution of resistance in the insect.

Further information is available at DOI:10.1016/j.pestbp.2026.107206