Developmental changes of chromaffin cell secretory response to hypoxia studied in thin adrenal slices

Abstract

Adrenomedullary chromaffin (AMC) cells are sensitive to hypoxia in the newborn, but whether this property is lost during postnatal maturation is a matter of controversy. We have developed a rat adrenal slice preparation that allows the study of neonatal and adult AMC cell sensitivity to hypoxia in almost optimal physiological conditions. Responses to secretagogues can be quantitatively and noninvasively monitored in intact cells by amperometry. We have found hypoxia "responsive" (R) and "non-responsive" AMC cells in both neonatal (P0-P8) and juvenile/adult (P12-P60) adrenal glands. However, in the neonate, the proportion of R cells and the magnitude of the response to hypoxia were larger than in the adult. This developmental change of hypoxia responsiveness did not seem to depend on a decrease of the AMC cell's excitability. Spontaneous secretory activity in slices from adult rats was even increased with respect to neonatal animals. The analysis of the secretory events suggests that changes in spike frequency, rather than in vesicle size, account for the increased basal secretion rate in adult AMC cells. Thus, we report a major, but not complete, loss of direct hypoxia sensitivity in adult AMC cells. The adrenal slice appears to be a valuable technique to study acute O(2) sensing and its modifications in pathophysiological states.