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This Article Full Text Full Text (PDF) All Versions of this Article: 548/3/789    most recent 2003.039693v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ortega-Sáenz, P. Articles by López-Barneo, J. Search for Related Content PubMed PubMed Citation Articles by Ortega-Sáenz, P. Articles by López-Barneo, J.

Rotenone selectively occludes sensitivity to hypoxia in rat carotid body glomus cells

Patricia Ortega-Sáenz, Ricardo Pardal, María García-Fernández and José López-Barneo

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.

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