Chemically induced cardiotoxicity: Role of voltage dependent ion channels.

Chemicals pervade human environments, with> 350,000 synthetic compounds driving unintentional exposures and pollution-linked deaths exceeding those from infectious diseases or violence. This review discusses the mechanisms of chemically induced cardiotoxicity (including pesticides, pollutants, heavy metals, and chemotherapeutics), emphasizing modulation of voltage-gated ion channels in cardiomyocytes, which disrupts action potential (AP) dynamics, excitation-contraction coupling (ECC), and predisposes to arrhythmogenesis. Key currents, sodium (INa), calcium (ICaL, ICaT), and potassium (Ito, IKr, IK1), are differentially altered. Pyrethroid pesticides (e.g., deltamethrin) amplify late INa, prolong AP, and trigger afterdepolarizations. Organochlorines (e.g., aldrin) suppress peak INa; organophosphates, carbamates, and fungicides (e.g., tebuconazole) inhibit ICaL, INa, and K+ currents, often via oxidative stress. Glyphosate-based herbicides impair ICaL; rodenticides (e.g., phosphides) block K+ hERG channel, mimicking Brugada syndrome. Environmental pollutants lack direct ion-channel block properties evidence but provoke arrhythmias via inflammation/fibrosis (diesel exhaust), NO/redox inhibition (CO: INa, hERG, Kir), current enhancement (SO2: INa, Ito, ICaL), or ROS-CaMKII activation (particulate matter). Heavy metals attenuates channels class-specifically: Pb2+ (ICaL), Ni2+ (ICaT), Cd2+ (INa, ICaL), Hg2+ (Ito, ICaL); Se/Zn modulate K+/Ca2+ currents in deficiency/excess. Chemotherapeutics exacerbate cardiovascular risk: anthracyclines (e.g., doxorubicin) boost ICaL and RyR2 leak; platinums delay INa decay; TKIs (e.g., ibrutinib) broadly suppress currents kinase-dependently. Integrating in vitro/experimental molecular data, this review maps class-specific electrophysiological impacts in the heart, highlighting safety pharmacology's role in risk mitigation and informing therapeutic, regulatory, and public health strategies to safeguard cardiovascular resilience against pervasive chemical threats.