Insecticides Affecting Calcium Channels

Flubendiamide, a benzenedicarboxamide insecticide, also affects calcium channels. This insecticide induces unique symptomology in poisoned insects, showing a gradual contraction of the insect body. It is believed that flubendiamide induces intracellular Ca2+ release mediated by a calcium channel such as the ryanodine receptor resulting in the contraction of insect muscle (Tohnishi et al., 2005 Ebbinghaus-Kintscher et al., 2006 Nauen, 2006). 

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Flubendiamide is an example of a new chemical class of insecticides that have been termed phthalic acid diamides (Nauen 2006, Copping and Duke 2007). They are related to the alkaloid ryanodine, which is extracted from Ryania species. Ryanodine affects muscles by binding to calcium channels of the sarcoplasmic reticulum. Ca + ions act as intracellular messengers, and their flux is modulated by calcium channels of this type. The toxic action of ryanodine and synthetic insecticides related to it is due to the disturbance of calcium flux. 

The acute toxic properties of the chlorinated hydrocarbon insecticides in humans are qualitatively similar. These agents interfere with inactivation of the sodium channel in excitable membranes and cause rapid repetitive firing in most neurons. Calcium ion transport is also inhibited. These events affect repolarization and enhance the excitability of neurons. The major effect is central nervous stimulation. With DDT, tremor may be the first manifestation, possibly continuing on to convulsions, whereas with the other compounds convulsions often appear as the first sign of intoxication. There is no specific treatment for the acute intoxicated state, management being symptomatic. 

It is noteworthy that the inactivation of the Heliothis RyR at millimolar [Ca ] was prevented at all flubendiamide concentrations tested. This could plausibly explain the insecticidal mechanism since deactivation of calcium release channels at high [Ca ] would be essential to terminate the intracellular calcium transient (27). According to this hypothesis, ryanodine receptors would be fixed in the (sub)conductance conformation leading to calcium store depletion and, possibly, to subsequent activation of capacitative calcium entry through plasma membrane channels. This would override compensatory calcium removal mechanisms such as the sarcoplasmic Ca-ATPase (SERCA) activity and the sodium-calcium exchanger (NCX) in the plasma membrmie. The sustained high intracellular [Ca would finally lead to muscle contraction paralysis that is consistently observed in flubendiamide-affected lepidopteran larvae. 

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