Systematic Review of Calcium Channels and Intracellular Calcium Signaling: Relevance to Pesticide Neurotoxicity

Pesticides of different chemical classes exert their toxic effects on the nervous system by acting on the different regulatory mechanisms of calcium (Ca²⁺) homeostasis. Pesticides have been shown to alter Ca²⁺ homeostasis, mainly by increasing its intracellular concentration above physiological levels. The pesticide-induced Ca²⁺ overload occurs through two main mechanisms: the entry of Ca²⁺ from the extracellular medium through the different types of Ca²⁺ channels present in the plasma membrane or its release into the cytoplasm from intracellular stocks, mainly from the endoplasmic reticulum. It has also been observed that intracellular increases in the Ca²⁺ concentrations are maintained over time, because pesticides inhibit the enzymes involved in reducing its levels. Thus, the alteration of Ca²⁺ levels can lead to the activation of various signaling pathways that generate oxidative stress, neuroinflammation and, finally, neuronal death. In this review, we also discuss some proposed strategies to counteract the detrimental effects of pesticides on Ca²⁺ homeostasis.