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.
Thompson
Roger J
RJ
Department of Cellular and Structural Biology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. roger.thompson@uchsc.edu
Farragher
Suzanne M
SM
Cutz
Ernest
E
Nurse
Colin A
CA
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