Oxygen‐Sensing by Ion Channels and Mitochondrial Function in Carotid Body Glomus Cells

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Abstract
Carotid body glomus cells release transmitters in response to hypoxia due to the increase of excitability resulting from inhibition of O2‐regulated K+ channels. The mechanisms involved in the detection of changes of O2 tension are unknown. Inhibition of the mitochondrial electron transport chain (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 dosedependent manner. The effect of rotenone is not mimicked by complex I inhibitors acting on different sites. We have also generated a knock‐out mouse lacking SDHD, the small membrane‐anchoring protein of the succinate dehydrogenase (complex II) of the mitochondrial electron transport chain. Homozygous Sdhd−/− animals die at early embryonic stages. Heterozygous Sdhd+/− mice show a general, non‐compensated, deficiency of complex II activity, and abnormal enhancement of resting carotid body secretion rate due to decrease of K+ conductance and persistent Ca2+ influx into glomus cells. However, responsiveness to hypoxia of carotid bodies from Sdhd+/− mice remains intact. These data strongly suggest that sensitivity to hypoxia of carotid body glomus cells is not linked in a simple way to mitochondrial electron flow. Nevertheless, it is possible that a rotenone‐sensitive molecule critically participates in acute carotid body oxygen sensing.

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