Absrtact: Cardiovascular disease remains the leading cause of death worldwide. Previous studies have largely regarded immune cells as passive sources of inflammatory mediators, while paying insufficient attention to their intrinsic electrophysiological properties governed by ion channels and Ca2+ signaling. This review focuses on ion channels as upstream molecular switches that determine immune cell functional states, elucidating how they regulate membrane potential and intracellular Ca2+ dynamics to shape immune cell activation thresholds, effector intensity, phenotypic polarization, and spatial behavior, thereby constituting the core regulatory axis of the immune cell electrophysiological microenvironment. We then demonstrate how immune cells transmit their electrophysiological states to the myocardium through at least three distinct mechanisms: (1) Ca2+-dependent inflammatory mediator secretion remodeling cardiomyocyte ion channels; (2) direct electrocoupling between resident immune cells and the cardiac conduction system via Cx43 gap junctions; and (3) chronic immune activation progressively establishing arrhythmogenic substrates. We further illustrate how these electrophysiological mechanisms couple immune cell electrophysiological function to cardiac pathology across distinct disease contexts, including myocardial infarction, arrhythmias, and myocarditis. Finally, we discuss the translational potential of targeting immune cell ion channels as a therapeutic strategy for cardiac diseases, and identify key unresolved challenges. Research into immune cell electrophysiology holds significant implications for deepening our understanding of cardiac disease mechanisms and developing innovative therapeutic strategies. Keywords: Immune cell electrophysiology; Ion channels; Calcium signaling; Myocardial remodeling; Cardiac arrhythmia; Atrial fibrillation; Heart failure; Myocardial infarction