Cardiac endogenous transmitter system: molecular features, functions, and clinical implications

Abstract Transmitter systems are molecular networks that facilitate signal transmission between neurons or between neurons and effector cells. Well-established examples include the glutamatergic, cholinergic, GABAergic, dopaminergic, serotonergic, and histaminergic systems. Traditionally, the heart was thought to lack its own endogenous transmitter systems (ETSs). However, recent studies have identified several such systems within cardiomyocytes and cardiac pacemaker cells. This review focuses on the endogenous glutamatergic, cholinergic, and GABAergic systems in the heart, providing a comprehensive analysis of their molecular composition, electrophysiological functions, arrhythmogenic implications, and therapeutic potential. Based on these findings, this review proposes a transmitter-based model of cardiac bioelectric regulation and highlights innovative strategies for targeting ETSs to prevent and treat arrhythmias.