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.
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.
Sekizawa
Shin-Ichi
S
Department of Pharmacology, School of Medicine, GBSF Room 3617, 451 Health Sciences Drive, University of California Davis, Davis, CA 95616-0635, USA.
Joad
Jesse P
JP
Pinkerton
Kent E
KE
Bonham
Ann C
AC
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*
D026902:Potassium Channel Blockers; D014028:Tobacco Smoke Pollution; D019789:Tetraethylammonium; D015761:4-Aminopyridine