Amyloid beta peptides mediate physiological remodelling of the acute O2 sensitivity of adrenomedullary chromaffin cells following chronic hypoxia.
OBJECTIVE
The non-neurogenic response of the neonatal adrenal medulla is vital in cardiovascular and respiratory development and to the survival of newborns exposed to hypoxic stress. Here, we examined the acute hypoxic response of immortalised rat adrenomedullary chromaffin cells following exposure to chronic hypoxia (CH; 6% O(2) for 24 h).


METHODS
Ca(2+) and K(+) channel currents were recorded using by whole-cell patch-clamp.


RESULTS
Following incubation in CH, the acute O(2) sensitivity of K(+) current in immortalised adrenomedullary chromaffin (MAH) cells was enhanced due to a selective increase in the density of an O(2)-sensitive Ca(2+)-dependent K(+) current, secondary to ROS-mediated augmentation of voltage-gated Ca(2+) currents. The effect of CH on Ca(2+) currents was not additive to exogenous Abeta(1-40) and was blocked by the gamma-secretase inhibitors gamma-X and gamma-VI, demonstrating a role for amyloid beta peptide (AbetaP) production. Ca(2+) current enhancement was abolished in the presence of the transcription inhibitor actinomycin D but unaffected by the vacuolar H(+) ATPase inhibitor bafilomycin A1.


CONCLUSIONS
AbetaP production and transcriptional regulation during CH regulated the properties of a peripheral chemosensory cell, defining a role for these enigmatic peptides in the signalling pathway of a physiological response to CH in the developing cardiovascular system.
Brown
Stephen T
ST
Department of Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
Johnson
Rosalyn P
RP
Senaratne
Rhandi
R
Fearon
Ian M
IM
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D002461:Cell Line, Transformed; D019439:Chromaffin Cells / Q000378:metabolism*; D002908:Chronic Disease; D000860:Hypoxia / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats
D016229:Amyloid beta-Peptides; D015220:Calcium Channels; D015221:Potassium Channels; D010100:Oxygen