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 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.
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Division of Pathology, Department of Pediatric Laboratory Medicine, The Research Institute, The Hospital for Sick Children and University of Toronto, 555 University Avenue, Toronto, ON,, Canada M5G 1X8.
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D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000493:pharmacokinetics; D015220:Calcium Channels / Q000502:physiology; D002344:Carotid Body / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D002395:Catecholamines / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D048288:Imidazolines; D008168:Lung / Q000294:innervation / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D016877:Oxidants / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017933:Peripheral Nervous System / Q000737:chemistry / Q000166:cytology; D011188:Potassium / Q000493:pharmacokinetics; D011817:Rabbits; D019789:Tetraethylammonium / Q000494:pharmacology
D015220:Calcium Channels; D002395:Catecholamines; D018491:Dopamine Agonists; D048288:Imidazolines; D016877:Oxidants; D002104:Cadmium; D019789:Tetraethylammonium; D006861:Hydrogen Peroxide; D015761:4-Aminopyridine; C011775:(3,4-dihydroxyphenylamino)-2-imidazoline; D011188:Potassium; D002118:Calcium