Secondhand Smoke Decreased Excitability and Altered Action Potential Characteristics of Cardiac Vagal Neurons in Mice

Abstract

Background: Secondhand smoke (SHS), a major indoor pollutant, is a significant risk factor for cardiovascular morbidity and mortality including arrhythmias and sudden cardiac death. Exposure to SHS can produce autonomic imbalance, as evidenced by reduced heart rate variability (HRV)—a clinical metric of cardiac vagal regulation. Currently, the mechanisms through which SHS changes the vagal preganglionic neuronal inputs to the heart to produce this remains unknown.Objectives: To characterize the effect of SHS on both the excitability and action potential (AP) characteristics of anatomically identified cardiac vagal neurons (CVNs) in the nucleus ambiguus and examine whether SHS alters small conductance calcium-activated potassium (SK) channel activity of these CVNs.Methods: Adult male mice were exposed to four weeks of filtered air or SHS (3 mg/m3) 6 h/day, 5 day/week. Using patch-clamp recordings on identified CVNs in brainstem slices, we determined neuronal excitability and AP characteristics with depolarizing step- and ramp-current injections.Results: Four weeks of SHS exposure reduced spiking responses to depolarizing current injections and increased AP voltage threshold in CVNs. Perfusion with apamin (20 nM) magnified these SHS-induced effects, suggesting reduced SK channel activity may serve to minimize the SHS-induced decreases in CVNs excitability. Medium afterhyperpolarization (a measurement of SK channel activity) was smaller in the SHS group, further supporting a lower SK channel activity. AP amplitude, rise rate, fast afterhyperpolarization amplitude (a measurement of voltage-gated channel activity), and decay rate were higher in the SHS group at membrane voltages more positive to 0 mV, suggesting altered inactivation properties of voltage-dependent channels underlying APs.Discussion: SHS exposure reduced neuronal excitability of CVNs with compensatory attenuation of SK channel activity and altered AP characteristics. Neuroplasticity of CVNs could blunt regulatory cardiac vagal signaling and contribute to the cardiovascular consequences associated with SHS exposure, including reduced HRV.

Effects of chronic secondhand smoke exposure on cardiovascular regulation and the role of soluble epoxide hydrolase in mice

“…Our previous study showed that 4 weeks of SHS exposure, at the same concentration as the present study, resulted in a decreased neuronal input-output relationship of these cardiac vagal neurons (Sun et al, 2021). The reduced neuronal output is due to a higher voltage/current threshold required for action potential generation and lower spiking responses to depolarizing stimuli (Sun et al, 2021). This SHS exposure-induced decrease in neuronal output may be a general feature of particulate matter pollution as exposures to particulate matters in the form of iron-soot also decreased HRV and neuronal outputs of these cardiac vagal neurons (Pham et al, 2009).…”

“…Together, these data suggest that the parasympathetic nervous system may be more sensitive to SHS exposure with a faster onset and that continued exposure may further tip the balance of autonomic regulation towards more permanent dysfunction through activation of the sympathetic nervous system. The parasympathetic regulation of the heart is mediated by innervations from the cardiac vagal neurons located in the nucleus ambiguous (Corbett et al, 1999;Pham et al, 2009;Sun et al, 2021). Our previous study showed that 4 weeks of SHS exposure, at the same concentration as the present study, resulted in a decreased neuronal input-output relationship of these cardiac vagal neurons (Sun et al, 2021).…”

“…The parasympathetic regulation of the heart is mediated by innervations from the cardiac vagal neurons located in the nucleus ambiguous ( Corbett et al, 1999 ; Pham et al, 2009 ; Sun et al, 2021 ). Our previous study showed that 4 weeks of SHS exposure, at the same concentration as the present study, resulted in a decreased neuronal input-output relationship of these cardiac vagal neurons ( Sun et al, 2021 ). The reduced neuronal output is due to a higher voltage/current threshold required for action potential generation and lower spiking responses to depolarizing stimuli ( Sun et al, 2021 ).…”

“…Animals in the SHS group were exposed to SHS for 12 weeks, followed by 4 weeks of SHS cessation ('recovery' from smoke) to model the effects of a smokefree environment following SHS exposure. 3R4F cigarettes, an international standard reference cigarette for smoke research (Hamad et al, 2017), from the University of Kentucky Tobacco and Health Research Institute (Lexington, KY, United States) were used to generate sidestream cigarette smoke as a surrogate for SHS (Chen et al, 2008;Sekizawa et al, 2008;Wang et al, 2018;Sun et al, 2021). Two cigarettes at a time were smoked in a staggered fashion under Federal Trade Commission conditions at a rate of 1 puff/min (35 mL/puff, 2 s duration).…”

Deep Learning-Based Electrocardiograph in Evaluating Radiofrequency Ablation for Rapid Arrhythmia

“…Operating principle is to use a certain transient high voltage and strong current through the chest wall directly acting on the heart, so that most or even all of the myocardial cells instantaneous depolarization. The electrical activity of the heart stops instantly, so that the heart is redominated by the highest self-regulatory pacing point, namely, the sinus node, and the abnormal heart rhythm is transformed into the normal sinus rhythm [ 17 , 18 ]. Cardiac surgery mainly improves the abnormal function of the heart to return to normal rhythm by directly cutting the tissue used for sinus velocity generation [ 19 ].…”