Hydrogen sulfide is an oxygen sensor in the carotid body

There is considerable controversy surrounding the initial step that transduces a fall in PO2 into a physiological signal, i.e., the “oxygen sensor” in chemoreceptors. Initial studies on systemic and respiratory vessels suggested that the metabolism of hydrogen sulfide (H2S) could serve as the oxygen sensor. This model was subsequently extended to chemoreceptors in fish and tissues of other animals. In this model, constitutive production of biologically active H2S is offset by H2S oxidation; when oxygen availability falls, production of H2S exceeds metabolism, and the resultant increase in intracellular H2S initiates the appropriate physiological responses. This model is supported by observations that the effects of hypoxia and H2S are similar, if not identical in many tissues: hypoxic responses are inhibited by inhibitors of H2S biosynthesis and augmented by sulfur donating molecules, and the tipping point between H2S production and oxidation occurs at physiologically relevant PO2s. Recent studies from other laboratories support this mechanism of O2 sensing in the carotid body. This review summarizes information that supports the H2S metabolic hypothesis in these tissues with emphasis on the carotid chemoreceptors. Evidence suggesting that H2S is not involved in oxygen sensing in the carotid body is also critically evaluated.

► Oxygen-dependent metabolism of hydrogen sulfide is a fundamental oxygen sensing mechanism. ► Hydrogen sulfide is produced by all cells and metabolized at physiologically relevant PO2s. ► Enzymes for hydrogen sulfide biosynthesis are present in the carotid body. ► Exogenous hydrogen sulfide mimics hypoxic response of carotid body glomus cells. ► Hydrogen sulfide depolarizes glomus cells by closing potassium channels.