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 P(O2) 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 I(A)-type current. The delayed current had two components, a TEA-sensitive, Ca2+-dependent current and a component with tile kinetic behaviour of a delayed rectifier. 4. Both types of current were oxygen sensitive. The I(A)-type current was reduced by 27.4 ± 3.2% when the P(O2) 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.