Identification of TREK channels in mouse intracardiac ganglion neurons

ABSTRACT The intracardiac nervous system is a complex neural network formed by a diffuse plexus, the so-called intracardiac ganglion (ICG). These ganglia locally innervate and control heart function, but little is known about how ICG neuronal activity is regulated. While various ionic currents have been characterized in cardiac tissue, the expression and role of TREK channels in ICG neurons remain unexplored. TWIK-related K+ (TREK) channels, members of the two-pore domain potassium channel family, are essential regulators of neuronal membrane resting potential and excitability, with recognized neuroprotective functions. In this study, we have characterized different ionic currents present in mouse ICG neurons, including tetrodotoxin-sensitive Na⁺ currents, delayed K+ rectifiers, Ca+2-dependent K⁺ currents and A, H and M currents. Notably, we provide the first evidence of functional TREK channel expression in these neurons. Our findings suggest that TREK channels contribute to excitability control and cellular homeostasis in ICG neurons, underscoring their potential as therapeutic targets for cardiac disorders. KEY POINTS - This study provides the first evidence of functional TREK channel expression in ICG neurons. - Comprehensive profiling of ionic currents shaping excitability in ICG neurons. - Neuroprotective TREK channels might emerge as potential therapeutic targets for cardiac disorders. Competing Interest Statement The authors have declared no competing interest.