Selective modulation of membrane currents by hypoxia in intact airway chemoreceptors from neonatal rabbit
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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 micrometer 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 micrometer), suggesting the presence of both Ca2+-dependent (IK(Ca)) and Ca2+-independent (IK(V)) components. 3. Inward currents, carried by voltage-dependent Ca2+ channels and also, in occasional cells (approximately 11%), by TTX-sensitive Na+ channels, were also detected in intact NEB cells. 4. Hypoxia (PO2 = 15-20 mmHg) reduced the outward K+ current by approximately 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. 5. Diphenylene iodonium (DPI; 1 microM) suppressed outward K+ current by approximately 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 approximately 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.
