Exogenous H₂S enhances mice gastric smooth muscle tension through S‐sulfhydration of K_V4.3, mediating the inhibition of the voltage‐dependent potassium current

Abstract

These results suggest that exogenous H2 S sulfhydrates KV 4.3 to decrease the membrane potential, thereby enhancing the basal tension of gastric antral smooth muscle.

Role of Transient Receptor Potential Ankyrin 1 Ion Channel and Somatostatin sst4 Receptor in the Antinociceptive and Anti-inflammatory Effects of Sodium Polysulfide and Dimethyl Trisulfide

“…H 2 S was reported to contract murine gastric smooth muscle by persulfidation of KV 4.3 channels. Inhibition of KV 4.3 channels was reproducible in H293 cells and could be diminished by a reducing agent and a blocker of free thiol groups that prevent protein persulfidation ( 47 ). Ability of the organic trisulfide DMTS to inhibit voltage-gated K + channels could contribute to depolarization of peptidergic sensory neurons and SOM release from these cells.…”

Protein S‐sulfhydration by hydrogen sulfide in cardiovascular system

“…Liu et al found that H 2 S decreased the membrane potential, inhibited the fast inactivation component of the voltage‐dependent potassium channel current in gastric smooth muscle cells and promoted gastric motility, which was suppressed by KV4.3 knockdown. Meanwhile, KV4.3 was S‐sulfhydrated by H 2 S, which was attenuated by DTT (Liu et al, ) . All these data suggested that different cysteine sites might be S‐sulfhydrated in different cells, which have various effects responsible for physiological or pathological process.…”

H2S‐induced gastric fundus smooth muscle tension potentiation is mediated by the phosphoinositide 3‐kinase/Akt/endothelial nitric oxide synthase pathway

“…3). These results suggest that H 2 S-induced enhancement of smooth muscle tension might be related in part to H 2 S-mediated reductions in NO, because our previous studies have shown that the excitatory effect of H 2 S on the gastrointestinal smooth muscles is mediated by voltage-dependent potassium channels and L-type calcium channels (Liu et al 2014;Meng et al 2015). When endogenous H 2 S production was decreased by AOAA, a CBS inhibitor, gastric fundus smooth muscle tension decreased significantly; however, L-NAME significantly attenuated the effects of AOAA (Fig.…”

“…The enzymes catalysing NO and H 2 S generation coexist in gastric smooth muscles cells, and we observed that these two gaseous biological molecules exert opposing effects with respect to the regulation of gastric fundus smooth muscle tension in the present study. These results suggest that H 2 S-induced enhancement of smooth muscle tension might be related in part to H 2 S-mediated reductions in NO, because our previous studies have shown that the excitatory effect of H 2 S on the gastrointestinal smooth muscles is mediated by voltage-dependent potassium channels and L-type calcium channels (Liu et al 2014;Meng et al 2015). 2).…”

“…However, whether H 2 S participates in or handles a similar signal pathway is unclear, as are its effects on smooth muscle motility, which appear to depend on its location and concentration. For example, NaHS hyperpolarizes the cell membrane and induces relaxation via ATP-sensitive potassium channels and apamin-sensitive potassium channels in rat and human colons (Stark & Szurszewski, 1992;Stark et al 1993); however, our previous study demonstrated that H 2 S functions as an excitatory modulator in the gastric antrum by inhibiting voltage-dependent potassium channel currents (Jin et al 2000;Yu et al 2003;Liu et al 2014). It is obvious that, unlike NO, which has a specific downstream signal pathway, the H 2 S-induced mechanism of regulation of gastrointestinal motility must be diverse.…”