Developmental regulation of O(2) sensing in neonatal adrenal chromaffin cells from wild-type and NADPH-oxidase-deficient mice.
In mammals, adrenomedullary chromaffin cells (AMC) express a neutrophil-like NADPH oxidase and secrete catecholamines, which play a vital role in the ability of the neonate to survive hypoxic stress. To test whether NADPH oxidase functions as an O(2) sensor, and whether mouse AMC express a developmentally regulated O(2)-sensing mechanism similar to rats, we compared the effects of hypoxia on cultured AMC from wild-type (WT) and transgenic oxidase-deficient (OD) mice, lacking the gp91(phox) subunit of NADPH oxidase. Hypoxia ( pO(2) congruent with5 mmHg) caused a reversible inhibition of outward K(+) current by congruent with27% ( n=6) in WT and congruent with29% ( n=9) in OD neonatal (P1-P5) chromaffin cells. O(2)-sensitive K(+) currents included both Ca(2+)-dependent ( I(BK)) and a delayed rectifier-like K(+) current ( I(KV)). Additionally, hypoxia depolarized WT and OD chromaffin cells and caused reversible broadening of the action potential. Exposure of both WT and OD neonatal AMC cultures to hypoxia (5% O(2)) for congruent with1 h caused four- to sixfold stimulation of catecholamine (CA) secretion as determined by HPLC. In contrast, hypoxia had no significant effect on K(+) currents or CA secretion in juvenile (P14-P15) AMC. Thus, mouse AMC possess a developmentally regulated O(2)-sensing mechanism, but NADPH oxidase does not function as the primary O(2)sensor in these cells.
Department of Cellular and Structural Biology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. roger.thompson@uchsc.edu
Roger J
RJ
Thompson
Suzanne M
SM
Farragher
Ernest
E
Cutz
Colin A
CA
Nurse
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002395:Catecholamines / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004594:Electrophysiology; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000172:deficiency*; D010100:Oxygen / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*
D002395:Catecholamines; D019255:NADPH Oxidases; D011188:Potassium; D010100:Oxygen