Hydrogen sulfide increases calcium-activated potassium (BK) channel activity of rat pituitary tumor cells

Abstract

Hydrogen sulfide (H(2)S) is the third gasotransmitter found to be produced endogenously in living cells to exert physiological functions. Large conductance (maxi) calcium-activated potassium channels (BK), which play an important role in the regulation of electrical activity in many cells, are targets of gasotransmitters. We examined the modulating action of H(2)S on BK channels from rat GH(3) pituitary tumor cells using patch clamp techniques. Application of sodium hydrogen sulfide as H(2)S donor to the bath solution in whole cell experiments caused an increase of calcium-activated potassium outward currents. In single channel recordings, H(2)S increased BK channel activity in a concentration-dependent manner. Hydrogen sulfide induced a reversible increase in channel open probability in a voltage-dependent, but calcium independent manner. The reducing agent, dithiothreitol, prevented the increase of open probability by H(2)S, whereas, the oxidizing agent thimerosal increased channel open probability in the presence of H(2)S. Our data show that H(2)S augments BK channel activity, and this effect can be linked to its reducing action on sulfhydryl groups of the channel protein.

Novel mechanism of hydrogen sulfide-induced guinea pig urinary bladder smooth muscle contraction: role of BK channels and cholinergic neurotransmission

“…Indeed, our results agree with previous reports showing that H 2 S directly inhibits BK channels in various types of cells treated with NaHS or gas-bubbled solutions containing dissolved H 2 S gas (31,46). Contrary to our findings, other studies showed that H 2 S augments whole cell currents in mouse tracheal smooth muscle (25) and increases BK channels open probability in rat pituitary tumor cells (44). The H 2 S effects have been demonstrated to be cell/tissue specific (47).…”

Hydrogen sulfide dilates rat mesenteric arteries by activating endothelial large-conductance Ca2+-activated K+ channels and smooth muscle Ca2+ sparks

“…As noted above, some studies suggest H 2 S activates the channel (7,15,17,28,34), whereas others find H 2 S inhibits BK Ca activity (13,30,31). Because the cell types in these two groups of studies do not overlap, it is possible that tissue-specific expression of subunits or other associated proteins modify the effect of H 2 S on BK Ca channels.…”

BK Channels – Focus on Polyamines, Ethanol/Acetaldehyde and Hydrogen Sulfide (H2S)

“…Sodium hydrosulfide (NaHS) was used as H 2 S donor since it can be readily handled and quantified. Our experiments showed that H 2 S dose-dependently increased single channel open probability (P open ) (Sitdikova et al 2010). In our cell free, single channel recordings where Ca 2+ is kept constant the increase of BK channel activity indicates that H 2 S does not act via elevation of the Ca 2+ concentration.…”

“…We choose GH3 cells since they are widely used as model cells to investigate BK channel activity in natural settings (Sitdikova et al 2010). Sodium hydrosulfide (NaHS) was used as H 2 S donor since it can be readily handled and quantified.…”