title: Oxygen-sensing mechanisms are present in the chromaffin cells of the sheep adrenal medulla before birth.
abstract: 1. The ability of the fetal adrenal medulla to respond directly to hypoxaemia and secrete catecholamines before the development of a functional innervation of the gland is essential for intrauterine survival. The cellular mechanisms involved in this response to low PO2 are not known, although the presence of oxygen-sensitive K+ channels in carotid body chemoreceptor cells and other sites suggests that these might underlie the chromaffin cell response. 2. Whole-cell patch-clamp techniques have been used to study K+ currents during normoxia and hypoxia in chromaffin cells isolated from the adrenal glands of fetal sheep. 3. Two types of chromaffin cells were observed, those with a fast inactivating K+ current and a larger capacitance and those with a delayed K+ current and smaller capacitance. No cell showed both types of current. The fast inactivating current showed voltage-dependent inactivation and was blocked by 1 mM 4-aminopyridine, characteristics of an IA-type current. The delayed current had two components, a TEA-sensitive, Ca2+-dependent current and a component with the kinetic behaviour of a delayed rectifier. 4. Both types of current were oxygen sensitive. The IA-type current was reduced by 27.4 +/- 3.2 % when the PO2 was reduced to about 15 mmHg. With the delayed current, hypoxia reduced the amplitude by 26.9 +/- 2.4 %, largely by reduction of the Ca2+-dependent component. 5. In the presence of hypoxia, reduction in the amplitude of these oxygen-sensitive K+ currents would increase the frequency and duration of action potentials, leading to increased activation of the L-type Ca2+ channels, influx of Ca2+ and the subsequent secretion of catecholamines.
authors.affiliation: Department of Physiology, University of Adelaide, Adelaide 5005, Australia.
authors.forename: G Y
authors.initials: GY
authors.lastname: Rychkov
authors.forename: M B
authors.initials: MB
authors.lastname: Adams
authors.forename: I C
authors.initials: IC
authors.lastname: McMillen
authors.forename: M L
authors.initials: ML
authors.lastname: Roberts
mesh_terms: D000311:Adrenal Glands / Q000166:cytology; D000313:Adrenal Medulla / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D020746:Calcium Channels, L-Type; D002344:Carotid Body / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000502:physiology*; D019439:Chromaffin Cells / Q000737:chemistry / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D011247:Pregnancy; D011950:Receptors, Cholinergic / Q000502:physiology; D012756:Sheep
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D011950:Receptors, Cholinergic; D010100:Oxygen