Hydrogen sulfide and hypoxia-induced changes in TASK (K2P3/9) activity and intracellular Ca2+ concentration in rat carotid body glomus cells

• H2S inhibited TASK activity, caused depolarization and elevated intracellular [Ca]i in carotid body glomus cells.
• Inhibitors of cystathionine-β-synthase and cystathionine-γ-lyase abolished the production of H2S in glomus cells.
• However, the inhibitors of these enzymes failed to block hypoxia-induced inhibition of TASK activity, depolarization or the elevation of intracellular [Ca]i.
• Thus, our results show that the level of endogenously produced H2S by hypoxia is not sufficiently high to cause glomus cell excitation, and that under normal conditions, a signal other than H2S mediates the hypoxia-induced excitation of glomus cells.

Acute hypoxia depolarizes carotid body chemoreceptor (glomus) cells and elevates intracellular Ca2+ concentration ([Ca2+]i). Recent studies suggest that hydrogen sulfide (H2S) may serve as an oxygen sensor/signal in the carotid body during acute hypoxia. To further test such a role for H2S, we studied the effects of H2S on the activity of TASK channel and [Ca2+]i, which are considered important for mediating the glomus cell response to hypoxia. Like hypoxia, NaHS (a H2S donor) inhibited TASK activity and elevated [Ca2+]i. To inhibit the production of H2S, glomus cells were incubated (3 h) with inhibitors of cystathionine-β-synthase and cystathionine-γ-lyase (dl-propargylglycine, aminooxyacetic acid, β-cyano-l-alanine; 0.3 mM). SF7 fluorescence was used to assess the level of H2S production. The inhibitors blocked L-cysteine- and hypoxia-induced elevation of SF7 fluorescence intensity. In cells treated with the inhibitors, hypoxia produced an inhibition of TASK activity and a rise in [Ca2+]i, similar in magnitude to those observed in control cells. L-cysteine produced no effect on TASK activity or [Ca2+]i and did not affect hypoxia-induced inhibition of TASK and elevation of [Ca2+]i. These findings suggest that under normal conditions, H2S is not a major signal in hypoxia-induced modulation of TASK channels and [Ca2+]i in isolated glomus cells.