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

1 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. 2 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 (I_K(Ca)) and Ca²⁺-independent (I_K(V)) components. 3 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. 4 Hypoxia (P${}_{\text{O}{}_{\text{2}}}$= 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 I_K(Ca) and I_K(V) components of outward current, and no further inhibition of K⁺ currents was seen with either TEA and 4-AP + hypoxia. 5 Diphenylene iodonium (DPI; 1 μm) suppressed outward K⁺ current by ∼42%, and DPI + hypoxia had no additional effect on the K⁺ current. 6 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%. 7 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.