Abstract
abstract Hydrogen sulfide (H2S) is produced endogenously in many types of mammalian cells. Evidence is now accumulating to suggest that H2S is an endogenous signalling molecule, with a variety of molecular targets, including ion channels. Here, we describe the effects of H2S on the large conductance, calcium-sensitive potassium channel (BKCa). This channel contributes to carotid body glomus cell excitability and oxygen-sensitivity. The experiments were performed on HEK 293 cells, stably expressing the human BKCa channel α subunit, using patch-clamp in the inside-out configuration. The H2S donor, NaSH (100µM–10 mM), inhibited BKCa channels in a concentration-dependent manner with an IC50 of ca. 670μM. In contrast to the known effects of CO donors, the H2S donor maximally decreased the open state probability by over 50% and shifted the half activation voltage by more than +16mV. In addition, although 1 mM KCN completely suppressed CO-evoked channel activation, it was without effect on the H2S-induced channel inhibition, suggesting that the effects of CO and H2S were non-competitive. RT-PCR showed that mRNA for both of the H2S-producing enzymes, cystathionine-beta-synthase and cystathionine-gamma-lyase, were expressed in HEK 293 cells and in rat carotid body. Furthermore, immunohistochemistry was able to localise cystathionine-gamma-lyase to glomus cells, indicating that the carotid body has the endogenous capacity to produce H2S. In conclusion, we have shown that H2S and CO have opposing effects on BKCachannels, suggesting that these gases have separate modes of action and that they modulate carotid body activity by binding at different motifs in the BKCaαsubunit.
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Telezhkin, V., Brazier, S., Cayzac, S., Müller, C., Riccardi, D., Kemp, P. (2009). Hydrogen Sulfide Inhibits Human BKCa Channels. In: Gonzalez, C., Nurse, C.A., Peers, C. (eds) Arterial Chemoreceptors. Advances in Experimental Medicine and Biology, vol 648. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2259-2_7
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DOI: https://doi.org/10.1007/978-90-481-2259-2_7
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