Second hand smoke exposure depresses neuronal excitability and enhances 4‐AP sensitive channel function of cardiac vagal neurons in the nucleus ambiguus

Abstract

BACKGROUNDSecond hand smoke (SHS) is a significant risk factor for cardiac dysfunction including arrhythmias and sudden cardiac death. Previously we showed that environmentally relevant concentrations of SHS reduce heart rate variability (HRV), an index of autonomic function. We also showed that SHS exposure significantly reduces cardiac vagal neuronal excitability in the nucleus ambiguus (NA), the final vagal cardiac output regulating HRV. We further showed that SHS‐induced attenuation of SK channel activity that may serve as a partial compensatory mechanism to the reduction in overall neuronal excitability. Here, we sought to test the hypothesis that SHS exposure, at an environmentally relevant concentration that reduces HRV, depresses neuronal excitability of cardiac vagal neurons in the NA by enhancing 4‐AP sensitive potassium channel function.METHODSAdult male C57BL6/J mice underwent open chest surgeries to retrograde label cardiac vagal neurons by applying a fluorescent dye (DiI) to the sinoatrial node. After two weeks of recovery from surgery, mice were randomly assigned to either filtered air (FA) or SHS (3 mg/m3, 6 hr/d, 5 d/wk) for 4‐, 8‐ or 12‐weeks. Whole‐cell current clamp recordings in brainstem slices were performed on anatomically identified cardiac vagal neurons in the NA with fluorescent labeling.RESULTSSHS exposure significantly (p < 0.05) reduced spiking response to depolarizing current injections after 4‐ and 12‐weeks – but not 8‐weeks – of exposure. Perfusion with 1 mM of 4‐AP, a voltage‐activated potassium channel blocker, similarly increased spiking response by 5–10 spikes/s across all time points. The 4‐AP induced changes in spiking responses were not different between SHS and FA (p > 0.05). SHS exposure also significantly (p < 0.05) increased voltage and current threshold for action potential generation for all time points tested (4‐, 8‐, and 12‐weeks). 4‐AP significantly lowered the voltage threshold; these effects were significantly (p < 0.05) bigger in the SHS group (−1.2 ± 0.5 mV vs. −3.7 ± 0.4 mV, FA vs. SHS respectively). In contrast, 4‐AP similarly lowered current threshold for action potential generation in both FA and SHS groups (−80 ± 13 pA vs. −103 ± 12 pA, FA vs. SHS, respectively).CONCLUSIONSWe conclude that environmentally relevant SHS exposure induces time‐dependent changes in neuronal excitability of cardiac vagal neurons. Some of these changes may be the result of increased voltage‐activated potassium channel function.Support or Funding InformationR01 ES025229; T32 HL086350This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.