Rotenone selectively occludes sensitivity to hypoxia in rat carotid body glomus cells.
Carotid body glomus cells release transmitters in response to hypoxia due to the increase of excitability resulting from inhibition of O2 -regulated K+ channels. However, the mechanisms involved in the detection of changes of O2 tension are unknown. We have studied the interaction between glomus cell O2 sensitivity and inhibition of the mitochondrial electron transport chain (ETC) in a carotid body thin slice preparation in which catecholamine release from intact single glomus cells can be monitored by amperometry. Inhibition of the mitochondrial ETC at proximal and distal complexes induces external Ca2+-dependent catecholamine secretion. At saturating concentration of the ETC inhibitors, the cellular response to hypoxia is maintained. However, rotenone, a complex I blocker, selectively occludes the responsiveness to hypoxia of glomus cells in a dose-dependent manner. The effect of rotenone is mimicked by 1-methyl-4-phenylpyridinium ion (MPP+), an agent that binds to the same site as rotenone, but not by complex I inhibitors acting on different sites. In addition, the effect of rotenone is not prevented by incubation of the cells with succinate, a substrate of complex II. These data strongly suggest that sensitivity to hypoxia of carotid body glomus cells is not linked in a simple way to mitochondrial electron flow and that a rotenone (and MPP+)-sensitive molecule critically participates in acute oxygen sensing in the carotid body.
Ortega-Sáenz
Patricia
P
Laboratorio de Investigaciones Biomédicas, Departamento de Fisiología and Hospital Universitario Virgen del Rocío, Universidad de Sevilla, E-41013, Seville, Spain.
Pardal
Ricardo
R
García-Fernandez
María
M
López-Barneo
José
J
D000818:Animals; D002344:Carotid Body / Q000187:drug effects / Q000502:physiology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D004579:Electron Transport / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012402:Rotenone / Q000494:pharmacology*
D012402:Rotenone