Involvement of ionic channels in chemically-induced neurotoxicity: examples of different molecular mechanisms

Neurotoxicity is defined as “an adverse change in the structure or function of the nervous system that results from exposure to a chemical, biological or physical agent". lonic channels, transporters, receptors for neurotransmitters and neurohormones are the main modulators of neuronal activity. It is therefore to be expected that the interfering with these proteins induces significant and potentially damaging effects in these tightly regulated and highly responsive cells. The present research project has been focused on the study of the role of specific ionic channels and the main mechanisms involved regarding two cases of neurotoxicity, which were widely documented but not completely understood: 1) the potential neurotoxicity induced by SiO2 NP and 2) the one induced by OHP. This issue has been addressed by means of an integrated approach that combine electrophysiological recordings both at single cell level by using the patch clamp technique, and at population level by using multielectrode arrays (MEAs), as well as quantitative real-time polymerase chain reaction (qRT-PCR) and/or RNAseq for a trascriptome screening. Members of TRP channel family (TRPA1, TRPV1, TRPV4), two pore domain K+ (K2P) channel family, as well as connexins and pannexin-like channels, are the major components of the responses by SiO2 NP and OHP. In conclusion, the information presented here may be valuable, particularly for contributing to current knowledge on this subject mainly regarding cells of the nervous system, as some evidence and mechanistic suggestions are provided.