Patients with cirrhosis often exhibit cardiac autonomic dysfunction (CAD), characterized by enhanced cardiac sympathetic activity and diminished cardiac vagal tone, leading to increased morbidity and mortality. This study delineates the cellular and molecular mechanisms associated with altered neuronal activities causing cirrhosis-induced CAD. Biliary and nonbiliary cirrhotic rats were produced by common bile duct ligation (CBDL) and intraperitoneal injections of thioacetamide (TAA), respectively. Three weeks after CBDL or TAA injection, the assessment of heart rate variability revealed autonomic imbalance in cirrhotic rats. We observed increased excitability in stellate ganglion (SG) neurons and decreased excitability in intracardiac ganglion (ICG) neurons in cirrhotic rats compared to sham-operated controls. Additionally, threshold, rheobase, and action potential duration exhibited opposite alterations in SG and ICG neurons, along with changes in afterhyperpolarization duration. A- and M-type K⁺ channels were significantly downregulated in SG neurons, while M-type K⁺ channels were upregulated, with downregulation of the N- and L-type Ca²⁺ channels in the ICG neurons of cirrhotic rats, both in transcript expression and functional activity. Collectively, these findings suggest that cirrhosis induces an imbalance between cardiac sympathetic and parasympathetic neuronal activities via the differential regulation of K⁺ and Ca²⁺ channels. Thus, cirrhosis-induced CAD may be associated with impaired autonomic efferent functions within the homeostatic reflex arc that regulates cardiac functions.

Airborne fine particulate matter (PM2.5) exposure is associated with central neuroinflammation and autonomic dysfunction, but its effects on peripheral sympathetic ganglia remain poorly defined. Here, we examined the effects of central PM2.5 administration and direct PM2.5 exposure on the superior cervical ganglion (SCG), a primary sympathetic relay governing cephalic noradrenergic outflow. Intracerebroventricular (ICV) administration of PM2.5 increased hypothalamic TNF-α and IL-6 levels and reduced presynaptic synaptophysin expression, while SCG tyrosine hydroxylase expression remained unchanged. In a complementary ex vivo model, direct PM2.5 exposure reduced norepinephrine (NE) accumulation in the culture medium of isolated SCGs without significantly altering tissue NE content. Mechanistically, live-cell Ca²⁺ imaging revealed attenuated depolarization-evoked Ca²⁺ responses in SCG neurons following either 24-h direct exposure or in vivo ICV administration. Whole-cell patch-clamp recordings further demonstrated reduced voltage-gated Ca²⁺ channel (VGCC) current density in neurons isolated from ICV PM2.5-treated rats. This functional reduction was not accompanied by significant changes in the SCG mRNA levels of the examined pore-forming Ca_vα1 subunits. In parallel, ICV PM2.5 administration increased GFAP and Kir4.1 protein levels and enhanced perineuronal GFAP immunoreactivity, consistent with satellite glial cell reactivity. Together, these findings identify impaired neuronal Ca²⁺ signaling and accompanying glial alterations in the SCG following PM2.5 exposure. The reductions in extracellular NE accumulation and VGCC function across complementary exposure models support a potential contribution of impaired Ca²⁺-dependent secretion to PM2.5-associated sympathetic dysfunction.