OXYGEN-SENSING MECHANISMS ARE PRESENT IN THE CHROMAFFIN CELLS OF THE SHEEP ADRENAL-MEDULLA BEFORE BIRTH

1. The ability of the fetal adrenal medulla to respond directly to hyp oxaemia and secrete catecholamines before the development of a functio nal innervation of the gland is essential for intrauterine survival. T he cellular mechanisms involved in this response to low P-O2 are not k nown, although the presence of oxygen-sensitive K+ channels in carotid body chemoreceptor cells and other sites suggests that these might un derlie the chromaffin cell response. 2. Whole-cell patch-clamp techniq ues 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 inactiv ating K+ current and a larger capacitance and those with a delayed Kcurrent and smaller capacitance. No cell showed both types of current. The fast inactivating current showed voltage-dependent inactivation a nd 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 the kinetic behaviour of a de layed 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 ampl itude by 26.9 +/- 2.4%, largely by reduction of the Ca2+-dependent com ponent. 5. In the presence of hypoxia, reduction in the amplitude of t hese oxygen-sensitive K+ currents would increase the frequency and dur ation of action potentials, leading to increased activation of the L-t ype C2+ and the subsequent secretion of catecholamines.