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

Eur J Neurosci. 2010 Feb;31(4):673-84. doi: 10.1111/j.1460-9568.2010.07093.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Action Potentials / drug effects*
  • Animals
  • Guinea Pigs
  • In Vitro Techniques
  • Lung / innervation*
  • Male
  • Membrane Potentials / drug effects
  • Neuroanatomical Tract-Tracing Techniques
  • Neurons, Afferent / metabolism
  • Neurons, Afferent / physiology*
  • Potassium Channel Blockers / pharmacology*
  • Random Allocation
  • Solitary Nucleus / drug effects*
  • Solitary Nucleus / metabolism
  • Solitary Nucleus / physiology*
  • Tetraethylammonium / pharmacology
  • Tobacco Smoke Pollution / adverse effects*

Substances

  • Potassium Channel Blockers
  • Tobacco Smoke Pollution
  • Tetraethylammonium
  • 4-Aminopyridine