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 mu m 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 (Cd(2+); 100 mu M), suggesting the presence of both Ca(2+) dependent (I(K(Ca))) and Ca(2+)-independent (I(K(V))) components. 3. Inward currents, carried by voltage-dependent Ca(2+) channels and also, in occasional cells (similar to 11%), by TTX-sensitive Na(+) channels, were also detected in intact NEB cells. 4. Hypoxia (P(o2) = 15-20 mmHg) reduced the outward K(+) current by similar to 34% during voltage steps from -60 to +30 mV, while inward Ca(2+) or Na(+) currents were not affected by hypoxia. Hypoxia suppressed roughly equally Tooth 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 mu M) suppressed outward K(+) current by similar to 42%, and DPI + hypoxia had no additional effect on the K(+) current. 6. Direct application of H(2)O(2) augmented outward K(+) current; for a voltage step from -60 mV to +30 mV, 0.25 mM H(2)O(2) increased K(+) current by similar to 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 O(2) chemoreceptors.