Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2023; 69(1): 25-34


M.I. Melnyk1,2, D.O. Dryn1, D.O. Dziuba3, A.V. Zholos2

  1. O.O. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
  2. ESC “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Ukraine
  3. Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine


The mechanisms of the negative consequences of general anaesthetics action on the nervous system have been studied in detail, but regarding smooth muscle function, such issues have not yet been sufficiently addressed. In this study, we investigated the effect of the general intravenous anaesthetic ketamine on the level of intracellular calcium in isolated ileum myocytes and the contractile activity of smooth muscle strips of the mouse small intestine. The concentration of intracellular calcium in cells was measured using the Ca2+-sensitive fluorescent dye Fura-2, and tensiometry was used to record the contractile activity of smooth muscles. It was shown that ketamine at a concentration of 100 µM significantly, by 40%, suppressed carbachol-induced contractile reactions of the ileum. The inhibitory effect correlated with the suppression of the intracellular calcium responses to carbachol in isolated smooth muscle cells after the addition of ketamine to the extracellular solution, which was by 65% on average. These results contribute to our better understanding of the possible membrane and intracellular mechanisms of the development of post-surgical intestinal motility disorders.

Keywords: smooth muscles; small intestine; general anesthesia; ketamine; calcium signaling; transient receptor potential channels; contraction recordings; TRPC4 channels agonist and antagonist.


  1. Zhou S, Liu J, Chen X-D. General anesthesia mediated by effects on ion channels. World J Crit Care Med. 2012 Jun 4;1(3):80-93. CrossRef PubMed PubMedCentral
  2. Brannigan G, LeBard DN, Hénin J, Eckenhoff RG, Klein ML. Multiple binding sites for the general anesthetic isoflurane identified in the nicotinic acetylcholine receptor transmembrane domain. Proc Natl Acad Sci USA. 2010 Aug10;107(32):14122-7. CrossRef PubMed PubMedCentral
  3. Nowacka A, Borczyk M. Ketamine applications beyond anesthesia - A literature review. Eur J Pharmacol. 2019 Oct 5;860:172547. CrossRef PubMed
  4. de Rocquigny G, Dubecq C, Martinez T, Peffer J, Cauet A, Travers S, Pasquier P. Use of ketamine for prehospital pain control on the battlefield: A systematic review. J Trauma Acute Care Surg. 2020 Jan;88(1):180-5). CrossRef PubMed
  5. Feder A, Costi S, Rutter SB, Collins AB, Govindarajulu U, Jha MK, et al. A randomized controlled trial of repeated ketamine administration for chronic posttraumatic stress disorder. Am J Psychiatr. 2021 Feb 1;178(2):193-202. CrossRef PubMed
  6. Liriano F, Hatten C, Schwartz TL. Ketamine as treatment for post-traumatic stress disorder: a review. Drugs Context. 2019Apr 8;8:212305. CrossRef PubMed PubMedCentral
  7. Melnyk MI, Dryn DO, Al Kury LT, Dziuba DO, Zholos A V. Suppression of mICAT in mouse small intestinal myocytes by general anaesthetic ketamine and its recovery by TRPC4 agonist (-)-englerin A. Front Pharmacol. 2020 Dec 18;11:594882. CrossRef PubMed PubMedCentral
  8. Wiryana M, Sinardja I, Budiart I, Gde T, Senapathi A, Widnyana M, et al. Low dose ketamin. Bali J Anesthesiol. 2022 Jan 1;1(1):13. CrossRef
  9. Berridge MJ. The inositol trisphosphate/calcium signaling pathway in health and disease. Physiol Rev. 2016 Oct 1;96(4):1261-96. CrossRef PubMed
  10. Bolton TB, Prestwich SA, Zholos AV, Gordienko DV. Excitation-contraction coupling in gastrointestinal and other smooth muscles. Annu Rev Physiol. 1999;61:85- CrossRef PubMed
  11. Dryn D, Melnyk M, Kizub I, Hu H, Soloviev A, Zholos A. The role of TRPV4 cation channels in the regulation of phenylephrine-induced contraction of rat pulmonary artery. Fiziol Zh. 2016;62(2):79-86. [Ukrainian]. CrossRef PubMed
  12. Boldyrev OI, Sotkis HV, Kuliieva IM, Vladymyrova IA, Filippov IB, Skryma R, et al. Expression of the cold receptor TRPM8 in the smooth muscles of the seminal ejaculatory ducts in rats. Fiziol Zh. 2009;55(5):17-27. [Ukrainian].
  13. Dryn D, Luo J, Melnyk M, Zholos A, Hu H. Inhalation anaesthetic isoflurane inhibits the muscarinic cation current and carbachol-induced gastrointestinal smooth muscle contractions. Eur J Pharmacol. 2018 Feb 5;820:39-44. CrossRef PubMed PubMedCentral
  14. Dresviannikov AV, Zholos AV, Shuba MF. Single nonselective cation channels activated by muscarinic agonists in smooth muscle cells of the guinea-pig small intestine. Fiziol Zh. 2004;50(4):85-91. [Ukrainian].
  15. Kindler CH, Eilers H, Donohoe P, Ozer S, Bickler PE. Volatile anesthetics increase intracellular calcium in cerebrocortical and hippocampal neurons. Anesthesiology. 1999 Apr;90(4):1137-45. CrossRef PubMed
  16. Zhu X, Yao Y, Guo M, Li J, Yang P, Xu H, Lin D. Sevoflurane increases intracellular calcium to induce mitochondrial injury and neuroapoptosis. Toxicol Lett. 2021 Jan 1;336:11-20. CrossRef PubMed
  17. Akata T, Izumi K, Nakashima M. Mechanisms of direct inhibitory action of ketamine on vascular smooth muscle in mesenteric resistance arteries. Anesthesiology. 2001 Aug;95(2):452-62. CrossRef PubMed
  18. Lubawski J, Saclarides TJ. Postoperative ileus: strategies for reduction. Ther Clin Risk Manag. 2008 Oct;4(5):913-7. CrossRef PubMed PubMedCentral
  19. Kohtala S. Ketamine-50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms. Pharmacol Rep. 2021 Apr 1;73(2):323-45. CrossRef PubMed PubMedCentral
  20. Hashimoto K. Rapid-acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective. Psychiatr Clin Neurosci. 2019 Oct 1;73(10):613-27. CrossRef PubMed PubMedCentral
  21. Feder A, Rutter SB, Schiller D, Charney DS. The emergence of ketamine as a novel treatment for posttraumatic stress disorder. Adv Pharmacol. 2020 Jan 1;89:261-86. CrossRef PubMed
  22. Yang LP, Jiang FJ, Wu GS, Deng K, Wen M, Zhou X, et al. Acute treatment with a novel TRPC4/C5 channel inhibitor produces antidepressant and anxiolytic-like effects in mice. PLoS One. 2015 Aug 28;10(8). CrossRef PubMed PubMedCentral
  23. Just S, Chenard BL, Ceci A, Strassmaier T, Chong JA, Blair NT, et al. Treatment with HC-070, a potent inhibitor of TRPC4 and TRPC5, leads to anxiolytic and antidepressant effects in mice. PLoS One. 2018 Jan 31;13(1):e0191225.23. CrossRef PubMed PubMedCentral
  24. Jeong B, Sung TS, Jeon D, Park KJ, Jun JY, So I, et al. Inhibition of TRPC4 channel activity in colonic myocytes by tricyclic antidepressants disrupts colonic motility causing constipation. J Cell Mol Med. 2022 May 12;00:1-13. CrossRef

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.