FIGURE 1.

Functional crosstalk between macrophages and cardiomyocytes. The schematic shows functional coupling between macrophages and cardiomyocytes through gap junctional channels. Small molecules including ATP are exchanged between cells with implications for inflammatory response. Macrophages have been shown to express ion channels that are similar to depolarizing (I_Ca, I_Na) and repolarizing mechanisms in heart (I_Kr, I_Ks, and I_K1). Previously Van Wagoner and others (Das et al., 2009), reported functional expression of Ca_v1.2 channels in macrophages, that could be blocked by known Ca channel blockers (amlodipine and verapamil), but were voltage-independent. Macrophages also express I_HERG-like currents, that are unrelated to cardiac I_Kr (Pennefather et al., 1998; Zhou et al., 1998), and inwardly rectifying K channels (Moreno et al., 2013; Kan et al., 2016). What role, if any do the expression of these channels play in mediating the effects of SFFAs on cardiac electrical activity? Despite the lack of clarity, macrophages are likely to influence cardiac electrical function to help maintain homeostatic control. This influence could be via direct (TL4R-cytokine release) or indirect (ATP-P2X7R) signaling pathways. Distinguishing between multiple pathways is likely to further illuminate the role of cardiac macrophages in inflammation and the pathogenesis of lipotoxic cardiomyopathy.