title: Secondhand smoke exposure alters K+ channel function and intrinsic cell excitability in a subset of second-order airway neurons in the nucleus tractus solitarius of young guinea pigs.
abstract: Extended exposure to secondhand smoke (SHS) in infants and young children increases the incidence of cough, wheeze, airway hyper-reactivity and the prevalence and earlier onset of asthma. The adverse effects may result from environmentally-induced plasticity in the neural network regulating cough and airway function. Using whole-cell patch-clamp recordings in brainstem slices containing anatomically identified second-order lung afferent neurons in the nucleus tractus solitarius (NTS), we determined the effects of extended SHS exposure in young guinea pigs for a duration equivalent to human childhood on the intrinsic excitability of NTS neurons. SHS exposure resulted in marked decreases in the intrinsic excitability of a subset of lung afferent second-order NTS neurons. The neurons exhibited a decreased spiking capacity, prolonged action potential duration, reduced afterhyperpolarization, decrease in peak and steady-state outward currents, and membrane depolarization. SHS exposure effects were mimicked by low concentrations of the K+ channel blockers 4-aminopyridine and/or tetraethyl ammonium. The data suggest that SHS exposure downregulates K+ channel function in a subset of NTS neurons, resulting in reduced cell excitability. The changes may help to explain the exaggerated neural reflex responses in children exposed to SHS.
authors.affiliation: Department of Pharmacology, School of Medicine, GBSF Room 3617, 451 Health Sciences Drive, University of California Davis, Davis, CA 95616-0635, USA.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Sekizawa
authors.forename: Jesse P
authors.initials: JP
authors.lastname: Joad
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
authors.forename: Ann C
authors.initials: AC
authors.lastname: Bonham
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000294:innervation*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D056347:Neuroanatomical Tract-Tracing Techniques; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011897:Random Allocation; D017552:Solitary Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D026902:Potassium Channel Blockers; D014028:Tobacco Smoke Pollution; D019789:Tetraethylammonium; D015761:4-Aminopyridine