AUTHOR=Sitdikova Guzel F. , Fuchs Roman , Kainz Verena , Weiger Thomas M. , Hermann Anton TITLE=Phosphorylation of BK channels modulates the sensitivity to hydrogen sulfide (H2S) JOURNAL=Frontiers in Physiology VOLUME=5 YEAR=2014 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2014.00431 DOI=10.3389/fphys.2014.00431 ISSN=1664-042X ABSTRACT=

Introduction: Gases, such as nitric oxide (NO), carbon monoxide (CO), or hydrogen sulfide (H₂S), termed gasotransmitters, play an increasingly important role in understanding of how electrical signaling of cells is modulated. H₂S is well-known to act on various ion channels and receptors. In a previous study we reported that H₂S increased calcium-activated potassium (BK) channel activity.

Aims: The goal of the present study is to investigate the modulatory effect of BK channel phosphorylation on the action of H₂S on the channel as well as to recalculate and determine the H₂S concentrations in aqueous sodium hydrogen sulfide (NaHS) solutions.

Methods: Single channel recordings of GH3, GH4, and GH4 STREX cells were used to analyze channel open probability, amplitude, and open dwell times. H₂S was measured with an anion selective electrode.

Results: The concentration of H₂S produced from NaHS was recalculated taking pH, temperature salinity of the perfusate, and evaporation of H₂S into account. The results indicate that from a concentration of 300 μM NaHS, only 11–13%, i.e., 34–41 μM is effective as H₂S in solution. GH3, GH4, and GH4 STREX cells respond differently to phosphorylation. BK channel open probability (Po) of all cells lines used was increased by H₂S in ATP-containing solutions. PKA prevented the action of H₂S on channel Po in GH4 and GH4 STREX, but not in GH3 cells. H₂S, high significantly increased Po of all PKG pretreated cells. In the presence of PKC, which lowers channel activity, H₂S increased channel Po of GH4 and GH4 STREX, but not those of GH3 cells. H₂S increased open dwell times of GH3 cells in the absence of ATP significantly. A significant increase of dwell times with H₂S was also observed in the presence of okadaic acid.

Conclusions: Our results suggest that phosphorylation by PKG primes the channels for H₂S activation and indicate that channel phosphorylation plays an important role in the response to H₂S.