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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.

SUBMITTER: Sun J

PROVIDER: S-EPMC8498211 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and objectivesActive smoking is associated with higher risk of various diseases. However, the risk of CKD development in nonsmokers exposed to secondhand smoke is not well elucidated. We aimed to investigate the association between secondhand smoke exposure and the risk of CKD development among never-smokers.Design, setting, participants, & measurementsA total of 131,196 never-smokers with normal kidney function, who participated in the Korean Genome and Epidemiology Study from 2001 to 2014, were analyzed. The participants were classified into three groups on the basis of frequency of secondhand smoke exposure, assessed with survey questionnaires; no exposure, <3 days per week, and ≥3 days per week. The association between secondhand smoke and CKD, defined as eGFR<60 ml/min per 1.73 m2, was examined in the cross-sectional analysis. In addition, the risk of incident CKD development was analyzed in a longitudinal cohort of 1948 participants without CKD at baseline, which was a subset of the main cohort.ResultsThe mean age of participants was 53 years, and 75% were women. Prevalent CKD was observed in 231 (1.8%), 64 (1.7%), and 2280 (2.0%) participants in the ≥3 days per week, <3 days per week, and no exposure groups. The odds ratio (OR) of prevalent CKD was significantly higher in the groups exposed to secondhand smoke than the no exposure group (<3 days per week: OR, 1.72; 95% confidence interval [95% CI], 1.30 to 2.27; and ≥3 days per week: OR, 1.44; 95% CI, 1.22 to 1.70). During a mean follow-up of 104 months, CKD occurred in 319 (16%) participants. Multivariable Cox analysis revealed that the risk for CKD development was higher in participants exposed to secondhand smoke than the no exposure group (<3 days per week: hazard ratio, 1.59; 95% CI, 0.96 to 2.65; and ≥3 days per week: hazard ratio, 1.66; 95% CI, 1.03 to 2.67).ConclusionsExposure to secondhand smoke was associated with a higher prevalence of CKD as well as development of incident CKD.

Project description:IntroductionDespite knowledge about major health effects of secondhand tobacco smoke (SHS) exposure, systematic incorporation of SHS screening and counseling in clinical settings has not occurred.MethodsA three-round modified Delphi Panel of tobacco control experts was convened to build consensus on the screening questions that should be asked and identify opportunities and barriers to SHS exposure screening and counseling. The panel considered four questions: (1) what questions should be asked about SHS exposure; (2) what are the top priorities to advance the goal of ensuring that these questions are asked; (3) what are the barriers to achieving these goals; and (4) how might these barriers be overcome. Each panel member submitted answers to the questions. Responses were summarized and successive rounds were reviewed by panel members for consolidation and prioritization.ResultsPanelists agreed that both adults and children should be screened during clinical encounters by asking if they are exposed or have ever been exposed to smoke from any tobacco products in their usual environment. The panel found that consistent clinician training, quality measurement or other accountability, and policy and electronic health records interventions were needed to successfully implement consistent screening.ConclusionsThe panel successfully generated screening questions and identified priorities to improve SHS exposure screening. Policy interventions and stakeholder engagement are needed to overcome barriers to implementing effective SHS screening.ImplicationsIn a modified Delphi panel, tobacco control and clinical prevention experts agreed that all adults and children should be screened during clinical encounters by asking if they are exposed or have ever been exposed to smoke from tobacco products. Consistent training, accountability, and policy and electronic health records interventions are needed to implement consistent screening. Increasing SHS screening will have a significant impact on public health and costs.

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

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