title: 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.affiliation: 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.
authors.forename: X W
authors.initials: XW
authors.lastname: Fu
authors.forename: C A
authors.initials: CA
authors.lastname: Nurse
authors.forename: Y T
authors.initials: YT
authors.lastname: Wang
authors.forename: E
authors.initials: E
authors.lastname: Cutz
mesh_terms: 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
chemical_list: 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