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EDITORIAL FOCUS

Expression of functional nicotinic acetylcholine receptors in neuroepithelial bodies of neonatal hamster lung

¹Division of Pathology, Department of Pediatric Laboratory Medicine, Research Institute, Hospital for Sick Children and University of Toronto, Toronto M5G 1X8; and ²Department of Biology, McMaster University, Hamilton, Ontario, Canada L8S 4K1

Submitted 8 April 2003 ; accepted in final form 20 June 2003

Pulmonary neuroepithelial bodies (NEB) are presumed airway chemoreceptors involved in respiratory control, especially in the neonate. Nicotine is known to affect both lung development and control of breathing. We report expression of functional nicotinic acetylcholine receptors (nAChR) in NEB cells of neonatal hamster lung using a combination of morphological and electrophysiological techniques. Nonisotopic in situ hybridization method was used to localize mRNA for the ₂-subunit of nAChR in NEB cells. Double-label immunofluorescence confirmed expression of ₄-, ₇-, and ₂-subunits of nAChR in NEB cells. The electrophysiological characteristics of nAChR in NEB cells were studied using the whole cell patch-clamp technique on fresh lung slices. Application of nicotine (0.1-100 µM) evoked inward currents that were concentration dependent (EC₅₀ = 3.8 µM; Hill coefficient = 1.1). ACh (100 µM) and nicotine (50 µM) produced two types of currents. In most NEB cells, nicotine-induced currents had a single desensitizing component that was blocked by mecamylamine (50 µM) and dihydro--erythroidine (50 µM). In some NEB cells, nicotine-induced current had two components, with fast- and slow-desensitizing kinetics. The fast component was selectively blocked by methyllcaconitine (MLA, 10 nM), whereas both components were inhibited by mecamylamine. Choline (0.5 mM) also induced an inward current that was abolished by 10 nM MLA. These studies suggest that NEB cells in neonatal hamster lung express functional heteromeric ₃₂, ₄₂, and ₇ nAChR and that cholinergic mechanisms could modulate NEB chemoreceptor function under normal and pathological conditions.

airway chemoreceptor; nicotinic acetylcholine ₃₂, ₄₂, and ₇ receptors; whole cell patch clamp; in situ hybridization; immunohistochemistry

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