Rat Adrenal Chromaffin Cells Are Neonatal CO2 Sensors

Abstract

We studied the participation of adrenal medulla (AM) chromaffin cells in hypercapnic chemotransduction. Using amperometric recordings, we measured catecholamine (CAT) secretion from cells inAMslices of neonatal and adult rats perfused with solutions bubbled with different concentrations of CO2. The secretory activity augmented from 1.74_0.19 pC/min at 5% CO2 to 6.36_0.77 pC/min at 10% CO2. This response to CO2 was dose dependent and appeared without changes in extracellular pH, although it was paralleled by a drop in intracellular pH. Responsiveness to hypercapnia was higher in neonatal than in adult slices. The secretory response to hypercapnia required extracellular Ca2_ influx. Both the CO2-induced internal pH drop and increase in CAT secretion were markedly diminished by methazolamide (2_M), a membrane-permeant carbonic anhydrase (CA) inhibitor.Wedetected the presence of twoCAisoforms (CAI and CAII) in neonatalAMslices by in situ hybridization and real-time PCR. The expression of these enzymes decreased in adultAMtogether with the disappearance of responsiveness to CO2. In patch-clamped chromaffin cells, hypercapnia elicited a depolarizing receptor potential, which led to action potential firing, extracellular Ca2_ influx, and CAT secretion. This receptor potential (inhibited by methazolamide) was primarily attributable to activation of a resting cationic conductance. In addition, voltage-gated K_ current amplitude was also decreased by high CO2. The CO2-sensing properties of chromaffin cells may be of physiologic relevance, particularly for the adaptation of neonates to extrauterine life, before complete maturation of peripheral and central chemoreceptors.