IL-1β augments H₂S-induced increase in intracellular Ca²⁺ through polysulfides generated from H₂S/NO interaction

H₂S has excitatory and inhibitory effects on Ca²⁺ signals via transient receptor potential ankyrin 1 (TRPA1) and ATP-sensitive K⁺ channels, respectively. H₂S converts intracellularly to polysulfides, which are more potent agonists for TRPA1 than H₂S. Under inflammatory conditions, changes in the expression and activity of these H₂S target channels and/or the conversion of H₂S to polysulfides may modulate H₂S effects. Effects of proinflammatory cytokines on H₂S-induced Ca²⁺ signals and polysulfide production in RIN14B cells were examined using fluorescence imaging with fura-2 and SSP4, respectively. Na₂S, a H₂S donor, induced 1) the inhibition of spontaneous Ca²⁺ signals, 2) inhibition followed by [Ca²⁺]_i increase, and 3) rapid [Ca²⁺]_i increase without inhibition in 50% (23/46), 22% (10/46), and 17% (8/46) of cells tested, respectively. IL-1β augmented H₂S-induced [Ca²⁺]_i increases, which were inhibited by TRPA1 and voltage-dependent L-type Ca²⁺ channel blockers. However, IL-1β treatment did not affect [Ca²⁺]_i increases evoked by a TRPA1 agonist or high concentration of KCl. Na₂S increased intracellular polysulfide levels, which were enhanced by IL-1β treatment. A NOS inhibitor suppressed the increased polysulfide production and [Ca²⁺]_i increase in IL-1β-treated cells. These results suggest that IL-1β augments H₂S-induced [Ca²⁺]_i increases via the conversion of H₂S to polysulfides through NO synthesis, but not via changes in the activity and expression of target channels. Polysulfides may play an important role in the effects of H₂S during inflammation.