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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/L892    most recent 00098.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fu, X. W. Articles by Cutz, E. Search for Related Content PubMed PubMed Citation Articles by Fu, X. W. Articles by Cutz, E.

Characterization of slowly inactivating KV current in rabbit pulmonary neuroepithelial bodies: effects of hypoxia and nicotine

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

Submitted 14 March 2007 ; accepted in final form 19 July 2007

Pulmonary neuroepithelial bodies (NEB) form innervated cell clusters that express voltage-activated currents and function as airway O₂ sensors. We investigated A-type K⁺ currents in NEB cells using neonatal rabbit lung slice preparation. The whole cell K⁺ current was slowly inactivating with activation threshold of –30 mV. This current was blocked 27% by blood-depressing substance I (BDS-I; 3 µM), a selective blocker of Kv3.4 subunit, and reduced 20% by tetraethylammonium (TEA; 100 µM). The BDS-I-sensitive component had an average peak value of 189 ± 14 pA and showed fast inactivation kinetics that could be fitted by one-component exponential function with a time constant of (1) 77 ± 10 ms. This Kv slowly inactivating current was also blocked by heteropodatoxin-2 (HpTx-2; 0.2 µM), a blocker of Kv4 subunit. The HpTx-2-sensitive current had an average peak value of 234 ± 23 pA with a time constant () 82 ± 11 ms. Hypoxia (PO₂ = 15–20 mmHg) inhibited the slowly inactivating K⁺ current by 47%, during voltage steps from –30 to +30 mV, and no further inhibition occurred when TEA was combined with hypoxia. Nicotine at concentrations of 50 and 100 µM suppressed the slowly inactivating K⁺ current by 24 and 40%, respectively. This suppression was not reversed by mecamylamine suggesting a direct effect of nicotine on these K⁺ channels. In situ hybridization experiments detected expression of mRNAs for Kv3.4 and Kv4.3 subunits, while double-label immunofluorescence confirmed membrane localization of respective channel proteins in NEB cells. These studies suggest that the hypoxia-sensitive current in NEB cells is carried by slowly inactivating A-type K⁺ channels, which underlie their oxygen-sensitive potassium currents, and that exposure to nicotine may directly affect their function, contributing to smoking-related lung disease.

Kv 3.4 and Kv4.3 currents; oxygen sensitive