Pathophysiological insights into ion channel dysregulation and electrical remodeling in cardiac cells during Trypanosoma cruzi infection.

Chagas disease (CD), caused by Trypanosoma cruzi, affects 6-7 million people globally. Its most severe form, chagasic cardiomyopathy (CCM), develops in ∼30 % of infected individuals after a long latency and is highly lethal, with sudden cardiac death responsible for most fatalities. CCM is fundamentally an arrhythmogenic cardiomyopathy marked by early and profound electrical remodeling driven by ion channel dysfunction, often preceding structural damage. Its pathogenesis is complex, emerging from parasite-host interactions that disrupt immune signaling, microvascular function, contractility, autonomic balance, and cellular electrophysiology. In this context, ion channel dysfunction becomes central, shaped directly by these pathogenic mechanisms and indirectly by metabolic alterations and the inflammatory/infectious milieu. This chapter explores the known ion channel abnormalities in CCM and their relationship to the inflammatory environment, detailing the roles of ion handling, oxidative stress, and metabolic disturbances in electrical remodeling. Parasite ion channels are also discussed as potential therapeutic targets.