Effects of iron-chelators on ion-channels and HIF-1alpha in the carotid body.
Acute hypoxia instantaneously increases the chemosensory discharge from the carotid body, increasing ventilation mostly by inhibiting the oxygen sensitive ion channels and exciting the mitochondrial functions in the glomus cells. On the other hand, Fe2+-chelation mimics hypoxia by inhibiting the prolyl hydroxylases and the degradation of HIF-1alpha in non-excitable cells. Whether Fe2+-chelation can inhibit the ion channels giving rise to the sensory responses in excitable cells was the question. We characterized the responses to Fe2+-chelators on excitable glomus cells of the rat, and found that they instantaneously blocked the ion-channels, exciting the chemosensory discharge, and later causing a gradual accumulation of HIF-1alpha. Although initiated by the same stimuli, the two effects (on ion channels and cytosolic HIF-1alpha) possibly occurred by two different mechanisms.
Roy
Arijit
A
Department of Physiology, University of Pennsylvania Medical Center, Philadelphia, PA 19104-6085, USA.
Li
Jingqing
J
Baby
Santhosh M
SM
Mokashi
Anil
A
Buerk
Donald G
DG
Lahiri
Sukhamay
S
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002344:Carotid Body / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007473:Ion Channels / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology*; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007473:Ion Channels; D007502:Iron Chelating Agents; D014157:Transcription Factors; D007501:Iron; D004298:Dopamine