Effect of Hydrogen Sulphide on Spontaneous Contractions of the Rat Jejunum. Role of KV-, KCa-, and Kir-Channels

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Abstract

In this work, we analyzed the role of voltage-gated (KV), calcium-activated (KCa), and inward-rectifier potassium channels (Kir) in the effects of hydrogen sulphide (H2S) donor sodium hydrosulphide (NaHS) on the spontaneous contractile activity of the rat jejunum. Experiments were performed on jejunum segments under isometric contraction conditions. It was shown that NaHS reduced the basal tension of the segments, the amplitude, and the frequency of spontaneous contractions in a dose-dependent manner (10–500 μM); the half-effective concentration (EC50) of the inhibitory effect of NaHS on amplitude was 165 μM. The KV channel blocker 4-AP (200 µM) increased the amplitude of spontaneous contractions and subsequent application of NaHS (200 μM) suppressed the amplitude and frequency of spontaneous activity as well as in the control; the effect on tonic tension was less pronounced. TEA (3 mM), a non-specific blocker, and paxillin (1 µM), a specific blocker of large conductance KСа (ВK) channels, increased the amplitude of spontaneous contractions, while the inhibitory effect of NaHS was completely preserved. The selective blocker of small conductance KCa (SK) channels NS8593 (4 μM) did not affect the tension and the parameters of spontaneous contractions and did not prevent the effects of NaHS. Diazoxide (100 μM), the opener of КATP channels, caused a decrease in the basal tone, the amplitude and frequency of spontaneous contractions. Diazoxide and KATP channel blocker glibenclamide (50 μM) prevented the effects of NaHS on the basal tone. The Kir-channel blocker BaCl2 (30 µM) increased the amplitude of spontaneous contractions and eliminated the inhibitory effects of NaHS on the frequency and amplitude of spontaneous contractions, and the basal tension decrease was less pronounced compared to control. Thus, a decrease in the tonic tension of a rat jejunum preparation under the action of an H2S donor is associated with the activation of Kir, including КATP channels, while the effects of H2S on the amplitude and frequency of spontaneous contractions are mediated by an increase in Ba2+-sensitive conductance.

About the authors

D. M. Sorokina

Kazan Federal University

Author for correspondence.
Email: dinagabita@mail.ru
Russia, 420008, Republic of Tatarstan, Kazan

I. F. Shaidullov

Kazan Federal University

Email: dinagabita@mail.ru
Russia, 420008, Republic of Tatarstan, Kazan

D. Buchareb

Kazan Federal University

Email: dinagabita@mail.ru
Russia, 420008, Republic of Tatarstan, Kazan

F. G. Sitdikov

Kazan Federal University

Email: dinagabita@mail.ru
Russia, 420008, Republic of Tatarstan, Kazan

G. F. Sitdikova

Kazan Federal University

Email: dinagabita@mail.ru
Russia, 420008, Republic of Tatarstan, Kazan

References

  1. Ситдикова Г.Ф., Зефиров А.Л. 2006. Газообразные посредники в нервной системе. Рос. физиол. журн. 92 (7), 872–882.
  2. Ситдикова Г.Ф., Зефиров А.Л. 2010. Сероводород: от канализаций Парижа к сигнальной молекуле. Природа. 9, 29–37.
  3. Ситдикова Г.Ф., Яковлев А.В., Зефиров А.Л. 2014. Газомедиаторы: от токсических эффектов к регуляции клеточных функций и использованию в клинике. Бюл. сибир. медицины. 13 (6), 185–200.
  4. Linden D.R. 2014. Hydrogen sulfide signaling in the gastrointestinal tract. Antioxid. Redox Signal. 20 (5), 818–830.
  5. Hermann A., Sitdikova G.F., Weiger T.M. 2012. Gasotransmitters: Physiology and Pathophysiology. Heidelberg: Springer. 204 p.
  6. Farrugia G., Szurszewski J.H. 2014. Carbon monoxide, hydrogen sulfide, and nitric oxide as signaling molecules in the gastrointestinal tract. Gastroenterology. 147 (2), 303–313.
  7. Gerasimova E., Lebedeva J., Yakovlev A., Zefirov A., Giniatullin R., Sitdikova G. 2015. Mechanisms of hydrogen sulfide (H2S) action on synaptic transmission at the mouse neuromuscular junction. Neuroscience. 303, 577–585.
  8. Cirino G., Szabo C., Papapetropoulos A. 2023. Physiological roles of hydrogen sulfide in mammalian cells, tissues, and organs. Physiol. Rev. 103 (1), 31–276.
  9. Singh P., Lembo A. 2021. Emerging role of the gut microbiome in irritable bowel syndrome. Gastroent. Clin. North Am. 50 (3), 523–545.
  10. Belizário J.E., Faintuch J., Garay-Malpartida M. 2018. Gut microbiome dysbiosis and immunometabolism: New frontiers for treatment of metabolic diseases. Mediators Inflamm. 2018, 2037838.
  11. Jimenez M., Gil V., Martinez-Cutillas M., Mañé N., Gallego D. 2017. Hydrogen sulphide as a signalling molecule regulating physiopathological processes in gastrointestinal motility. Br. J. Pharmacol. 174 (17), 2805–2817.
  12. Martin G.R., Mcknight G.W., Dicay M.S., Coffin C.S., Ferraz J.G.P., Wallace J.L. 2010. Hydrogen sulphide synthesis in the rat and mouse gastrointestinal tract. Dig. Liver. Dis. 42 (2), 103–109.
  13. Quan X., Luo H., Liu Y., Xia H., Chen W., Tang Q. 2015. Hydrogen sulfide regulates the colonic motility by inhibiting both L-type calcium channels and BKCa channels in smooth muscle cells of rat colon. PLoS One. 10 (3), e0121331.
  14. Hosoki R., Matsuki N., Kimura H. 1997. The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochem. Biophys. Res. Commun. 237 (3), 527–531.
  15. Gallego D., Clave P., Donovan J., Rahmati R., Grundy D., Jiménez M., Beyak M.J. 2008. The gaseous mediator, hydrogen sulphide, inhibits in vitro motor patterns in the human, rat and mouse colon and jejunum. Neurogastroenterol. Motil. 20 (12), 1306–1316.
  16. Teague B., Asiedu S., Moore P.K. 2002. The smooth muscle relaxant effect of hydrogen sulphide in vitro: Evidence for a physiological role to control intestinal contractility. Br. J. Pharmacol. 137 (2), 139–145.
  17. Nagao M., Duenes J.A., Sarr M.G. 2012. Role of hydrogen sulfide as a gasotransmitter in modulating contractile activity of circular muscle of rat jejunum. J. Gastrointest. Surg. 16 (2), 334–343.
  18. Gil V., Gallego D., Jiménez M. 2011. Effects of inhibitors of hydrogen sulphide synthesis on rat colonic motility. Br. J. Pharmacol. 164 (2 B), 485–498.
  19. Liu D.H., Huang X., Meng X.M., Zhang C.M., Lu H.L., Kim Y.C., Xu W.X. 2014. Exogenous H2S enhances mice gastric smooth muscle tension through S-sulfhydration of KV4.3, mediating the inhibition of the voltage-dependent potassium current. Neurogastroenter. Motil. 26 (12), 1705–1716.
  20. Zhao P., Huang X., Wang Z. 2009. Dual effect of exogenous hydrogen sulfide on the spontaneous contraction of gastric smooth muscle in guinea-pig. Eur. J. Pharmacol. 616 (1–3), 223–228.
  21. Shafigullin M.Y., Zefirov R.A., Sabirullina G.I., Zefirov A.L., Sitdikova G.F. 2014. Effects of a hydrogen sulfide donor on spontaneous contractile activity of rat stomach and jejunum. Bull. Exp. Biol. Med. 157 (3), 302–306.
  22. Dunn W.R., Alexander S.P.H., Ralevic V., Roberts R.E. 2016. Effects of hydrogen sulphide in smooth muscle. Pharmacol. Ther. 158, 101–113.
  23. Kasparek M.S., Linden D.R., Farrugia G., Sarr M.G. 2012. Hydrogen sulfide modulates contractile function in rat jejunum. J. Surg. Res. 175 (2), 234–242.
  24. Dhaese I., Van Colen I., Lefebvre R.A. 2010. Mechanisms of action of hydrogen sulfide in relaxation of mouse distal colonic smooth muscle. Eur. J. Pharmacol. 628 (1–3), 179–186.
  25. Shaidullov I.F., Shafigullin M.U., Gabitova D.M. 2018. Role of potassium channels in the effects of hydrogen sulfide on contractility of gastric smooth muscle cells in rats. J. Evol. Biochem. Phys. 54, 400–407.
  26. Gabitova D.M., Shaidullov I.F., Sabirullina G.I., Shafigullin M.U., Sitdikov F.G., Sitdikova G.F. 2017. Role of cyclic nucleotides in the effect of hydrogen sulfide on contractions of rat jejunum. Bull. Exp. Biol. Med. 163, 14–17.
  27. Han Y.F., Huang X., Guo X., Wu Y.S., Liu D.H., Lu H.L., Kim Y.C., Xu W.X. 2011. Evidence that endogenous hydrogen sulfide exerts an excitatory effect on gastric motility in mice. Eur. J. Pharmacol. 673 (1–3), 85–95.
  28. Huang X., Meng X.M., Liu D.H., Wu Y.S., Guo X., Lu H.L., Zhuang X.Y., Kim Y.C., Xu W.X. 2013. Different regulatory effects of hydrogen sulfide and nitric oxide on gastric motility in mice. Eur. J. Pharmacol. 720 (1–3), 276–285.
  29. Lu W., Li J., Gong L., Xo X., Han T., Ye Y., Che T., Luo Y., Li J., Zhan R., Yao W., Liu K., Cui S., Liu C. 2014. H2S modulates duodenal motility in male rats via activating TRPV1 and KATP channels. Br. J. Pharmacol. 171 (6), 1534–1550.
  30. Sanders K.M., Ward S.M., Koh S.D. 2014. Interstitial cells: Regulators of smooth muscle function. Physiol. Rev. 94 (3), 859–907.
  31. Sanders K.M., Ward S.M. 2019. Nitric oxide and its role as a non-adrenergic, non-cholinergic inhibitory neurotransmitter in the gastrointestinal tract. Br. J. Pharmacol. 176 (2), 212–227.
  32. Farrugia G. 1999. Ionic conductances in gastrointestinal smooth muscles and interstitial cells of Cajal. Annu. Rev. Physiol. 61, 45–84.
  33. Thornbury K.D., Ward S.M., Sanders K.M. 1992. Participation of fast-activating, voltage-dependent K currents in electrical slow waves of colonic circular muscle. Am. J. Physiol. – Cell Physiol. 263 (1), 226–236.
  34. Currò D. 2016. The modulation of potassium channels in the smooth muscle as a therapeutic strategy for disorders of the gastrointestinal tract. Adv. Protein Chem. Struct. Biol. 104, 263–305.
  35. Martelli A., Testai L., Breschi M.C., Lawson K., McKay N.G., Miceli F., Taglialatela M., Calderone V. 2013. Vasorelaxation by hydrogen sulphide involves activation of KV7 potassium channels. Pharmacol. Res. 70 (1), 27–34.
  36. Sitdikova G.F., Weiger T.M., Hermann A. 2010. Hydrogen sulfide increases calcium-activated potassium (BK) channel activity of rat pituitary tumor cells. Pflugers. Arch. 459 (3), 389–397.
  37. Sitdikova G.F., Fuchs R., Kainz V., Weiger T.M., Hermann A. 2014. Phosphorylation of BK channels modulates the sensitivity to hydrogen sulfide (H2S). Front. Physiol. 5, 431.
  38. Jackson-Weaver O., Osmond J.M., Riddle M.A., Naik J.S., Gonzalez Bosc L.V., Walker B.R., Kanagy N.L. 2013. Hydrogen sulfide dilates rat mesenteric arteries by activating endothelial large-conductance Ca2+-activated K+ channels and smooth muscle Ca2+ sparks. Am. J. Physiol. Heart Circ. Physiol. 304 (11), H1446–Y1454.
  39. Medina-Terol G.J., Huerta de la Cruz S., Beltran-Ornelas J.H., Sánchez-López A., Centurión D. 2022. Pharmacological evidence that potassium channels mediate hydrogen sulfide-induced inhibition of the vasopressor sympathetic outflow in pithed rats. Eur. J. Pharmacol. 931, 175160.
  40. Takir S., Ortaköylü G.Z., Toprak A., Uydeş-Doğan B.S. 2015. NaHS induces relaxation response in prostaglandin F2α precontracted bovine retinal arteries partially via K V and Kir channels. Exp. Eye. Res. 132, 190–197.
  41. Zhao W., Zhang J., Lu Y., Wang R. 2001. The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener. EMBO J. 20 (21), 6008–6016.
  42. Lowicka E., Beltowski J. 2007. Hydrogen sulfide (H2S) – the third gas of interest for pharmacologists. Pharmacol. Rep. 59 (1), 4–24.
  43. Furne J., Saeed A., Levitt M.D. 2008. Whole tissue hydrogen sulfide concentrations are orders of magnitude lower than presently accepted values. Am. J. Physiol. – Regul. Integr. Comp. Physiol. 295 (5).
  44. Kasparek M.S., Fatima J., Iqbal C.W., Duenes J.A., Sarr M.G. 2007. Role of VIP and substance P in NANC innervation in the longitudinal smooth muscle of the rat jejunum – influence of extrinsic denervation. J. Surg. Res. 141 (1), 22–30.
  45. Olson K.R. 2009. Is hydrogen sulfide a circulating “gasotransmitter” in vertebrate blood? Biochim. Biophys. Acta. – Bioenerg. 1787 (7), 856–863.
  46. Han Y., Shang Q., Yao J., Ji Y. 2019. Hydrogen sulfide: A gaseous signaling molecule modulates tissue homeostasis: Implications in ophthalmic diseases. Cell Death Dis. 10 (4), 1–12.
  47. Hall D.A., Langmead C.J. 2010. Matching models to data: A receptor pharmacologist’s guide. Br. J. Pharmacol. 161 (6), 1276–1290.
  48. Horowitz B., Ward S.M., Sanders K.M. 1999. Cellular and molecular basis for electrical rhythmicity in gastrointestinal muscles. Annu. Rev. Physiol. 61, 19–43.
  49. Schram G., Melnyk P., Pourrier M., Wang Z., Nattel S. 2002. Kir2.4 and Kir2.1 K+ channel subunits co-assemble: A potential new contributor to inward rectifier current heterogeneity. J. Physiol. 544 (2), 337–349.
  50. Hibino H., Inanobe A., Furutani K., MuraKami S., Findlay I., Kurachi Y. 2010. Inwardly rectifying potassium channels: Their structure, function, and physiological roles. Physiol. Rev. 90 (1), 291–366.
  51. Vogalis F. 2000. Potassium channels in gastrointestinal smooth muscle. J. Auton. Pharmacol. 20 (4), 207–219.
  52. Currò D. 2014. K+ channels as potential targets for the treatment of gastrointestinal motor disorders. Eur. J. Pharmacol. 733 (1), 97–101.
  53. Hatton W.J., Mason H.S., Carl A., Doherty P., Latten M.J., Kenyon J.L., Sanders K.M., Horowitz B. 2001. Functional and molecular expression of a voltage-dependent K+ channel (KV1.1) in interstitial cells of Cajal. J. Physiol. 533 (2), 315–327.
  54. Amberg G.C., Koh S.D., Imaizumi Y., Ohya S., Sanders K.M. 2003. A-type potassium currents in smooth muscle. Am. J. Physiol. Cell Physiol. 284 (3), C583–C595.
  55. Beyder A., Farrugia G. 2012. Targeting ion channels for the treatment of gastrointestinal motility disorders. Therap. Adv. Gastroenterol. 5 (1), 5–21.
  56. Grissmer S., Nguyen A.N., Aiyar J., Hanson D.C., Mather R.J., Gutman G.A., Karmilowicz M.J., Auperin D.D., Chandy K.G. 1994. Pharmacological characterization of five cloned voltage-gated K+-channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol. Pharmacol. 45 (6), 1227–1234.
  57. Schmalz F., Kinsella J., Koh S.D., Vogalis F., Schneider A., Flynn E.R., Kenyon J.L., Horowitz B. 1998. Molecular identification of a component of delayed rectifier current in gastrointestinal smooth muscles. Am. J. Physiol. 274 (5).
  58. Zhu Y., Huizinga J.D. 2008. Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channel. J Cell. Mol. Med. 12 (5A), 1718–1727.
  59. Hermann A., Sitdikova G.F., Weiger T.M. 2015. Oxidative stress and maxi calcium-activated potassium (BK) channels. Biomolecules. 5 (3), 1870.
  60. Hong S.J., Roan Y.F., Chang C.C. 1997. Spontaneous activity of guinea pig ileum longitudinal muscle regulated by Ca2+-activated K+ channel. Am. J. Physiol. 272 (5 Pt 1).
  61. Chen M.X., Gorman S.A., Benson B., Singh K., Hieble J.P., Michel M.C., Tate S.N., Trezise D.J. 2004. Small and intermediate conductance Ca2+-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum. Naunyn Schmiedeb. Arch. Pharmacol. 369 (6), 602–615.
  62. Neylon C.B., Nurgali K., Hunne B., Robbins H.L., Moore S., Chen M.X., Furness J.B. 2004. Intermediate-conductance calcium-activated potassium channels in enteric neurones of the mouse: Pharmacological, molecular and immunochemical evidence for their role in mediating the slow afterhyperpolarization. J. Neurochem. 90 (6), 1414–1422.
  63. Koh S.D., Sanders K.M., Carl A. 1996. Regulation of smooth muscle delayed rectifier K+ channels by protein kinase A. Pflügers. Arch. 432 (3), 401–412.
  64. Quan X., Chen W., Qin B., Wang J., Luo H., Dai F. 2022. The excitatory effect of hydrogen sulfide on rat colonic muscle contraction and the underlying mechanism. J. Pharmacol. Sci. 149 (3), 100–107.
  65. Huang X., Lee S.H., Lu H., Sanders K.M., Koh S.D. 2018. Molecular and functional characterization of inwardly rectifying K+ currents in murine proximal colon. J. Physiol. 596 (3), 379–391.
  66. Na J.S., Hong C., Kim M.W., Park C.G., Kang H.G., Wu M.J., Jiao H.Y., Choi S., Jun J.Y. 2017. ATP-sensitive K+ channels maintain resting membrane potential in interstitial cells of Cajal from the mouse colon. Eur. J. Pharmacol. 809, 98–104.
  67. Jiang B., Tang G., Cao K., Wu L., Wang R. 2010. Molecular mechanism for H2S-induced activation of KATP channels. Antioxid. Redox Signal. 12 (10), 1167–1178.
  68. Flynn E.R.M., McManus C.A., Bradley K.K., Koh S.D., Hegarty T.M., Horowitz B., Sanders K.N. 1999. Inward rectifier potassium conductance regulates membrane potential of canine colonic smooth muscle. J. Physiol. 518 (1), 247–256.
  69. Cheng Xiang G. 2017. Effects of NaOH, HCl and BaCl2 on contraction of smooth muscle in small intestine of rabbit. Genomics. Appl. Biol. 36 (12), 4953–4957.
  70. Lee J.Y., Ko E.J., Ahn K.D., Kim S., Rhee P.L. 2015. The role of K+ conductances in regulating membrane excitability in human gastric corpus smooth muscle. Am. J. Physiol. – Gastr. Liver. Physiol. 308 (7), G625–G633.
  71. Сорокина Д.М., Шайдуллов И.Ф., Гиззатуллин А.Р., Ситдиков Ф.Г., Ситдикова Г.Ф. 2023. Роль оксида азота и ионов кальция в эффектах сероводорода на сократительную активность тощей кишки крысы. Биофизика. 58 (4).
  72. Tang Q., Quan X., Yan L., Ren H., Chen W., Xia H., Luo H. 2018. Mechanism of sodium hydrosulfide modulation of L-type calcium channels in rat colonic smooth muscle cells. Eur. J. Pharmacol. 818, 356–363.

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