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

Abstract

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.

• Authors: X W Fu, C A Nurse, Y T Wang, E Cutz
• Journal: The Journal of physiology (J Physiol) Vol. 514 ( Pt 1) Pg. 139-50 (Jan 01 1999) ISSN: 0022-3751 [Print] England
• PMID: 9831722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channels
• Catecholamines
• Dopamine Agonists
• Imidazolines
• Oxidants
• Cadmium
• Tetraethylammonium
• Hydrogen Peroxide
• 4-Aminopyridine
• (3,4-dihydroxyphenylamino)-2-imidazoline
• Potassium
• Calcium

Topics

• 4-Aminopyridine (pharmacology)
• Animals
• Animals, Newborn
• Cadmium (pharmacology)
• Calcium (pharmacokinetics)
• Calcium Channels (physiology)
• Carotid Body (chemistry, cytology, physiology)
• Catecholamines (pharmacology)
• Dopamine Agonists (pharmacology)
• Female
• Hydrogen Peroxide (pharmacology)
• Hypoxia (physiopathology)
• Imidazolines
• Lung (innervation, physiology)
• Male
• Membrane Potentials (drug effects, physiology)
• Organ Culture Techniques
• Oxidants (pharmacology)
• Patch-Clamp Techniques
• Peripheral Nervous System (chemistry, cytology)
• Potassium (pharmacokinetics)
• Rabbits
• Tetraethylammonium (pharmacology)