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Selective modulation of membrane currents by hypoxia in intact airway chemoreceptors from neonatal rabbit

By Xiao Wen Fu, Colin A Nurse, Yu Tian Wang and Ernest Cutz

Abstract

We previously described voltage-dependent ionic currents and hypoxia chemosensitivity in cultured pulmonary neuroepithelial body (NEB) cells isolated from fetal rabbit. Here we use fresh neonatal rabbit lung slices (200–400 μm thick) to characterize the electrophysiological properties of ‘intact’ NEBs with patch-clamp, whole-cell recording.Under voltage clamp, outward currents were partially inhibited by TEA (20 mm), 4-amino pyridine (4-AP; 2 mm) and cadmium (Cd2+; 100 μm), suggesting the presence of both Ca2+-dependent (IK(Ca)) and Ca2+-independent (IK(V)) components.Inward currents, carried by voltage-dependent Ca2+ channels and also, in occasional cells (∼11%), by TTX-sensitive Na+ channels, were also detected in intact NEB cells.Hypoxia (PO2= 15–20 mmHg) reduced the outward K+ current by ∼34% during voltage steps from −60 to +30 mV, while inward Ca2+ or Na+ currents were not affected by hypoxia. Hypoxia suppressed roughly equally both IK(Ca) and IK(V) components of outward current, and no further inhibition of K+ currents was seen with either TEA and 4-AP + hypoxia.Diphenylene iodonium (DPI; 1 μm) suppressed outward K+ current by ∼42%, and DPI + hypoxia had no additional effect on the K+ current.Direct application of H2O2 augmented outward K+ current; for a voltage step from −60 mV to +30 mV, 0.25 mm H2O2 increased K+ current by ∼37%.These results indicate that intact neonatal NEB cells express hypoxic chemosensitivity and introduce the rabbit lung slice preparation as an new model for investigating the role of airway O2 chemoreceptors

Topics: Research Papers
Publisher: Blackwell Science Inc
OAI identifier: oai:pubmedcentral.nih.gov:2269045
Provided by: PubMed Central
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