TY - JOUR
T1 - 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
AU - Sekizawa, Shin Ichi
AU - Joad, Jesse P.
AU - Pinkerton, Kent E
AU - Bonham, Ann C.
PY - 2010/2
Y1 - 2010/2
N2 - 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.
AB - 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.
KW - Airway afferent fibers
KW - Environmental air pollutants
KW - Intrinsic cell excitability
KW - Ion channels
KW - K currents
KW - Postsynaptic neurons
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U2 - 10.1111/j.1460-9568.2010.07093.x
DO - 10.1111/j.1460-9568.2010.07093.x
M3 - Article
C2 - 20384811
AN - SCOPUS:76949091365
VL - 31
SP - 673
EP - 684
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
SN - 0953-816X
IS - 4
ER -