ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 23 of 42
JMBS 2020, 5(2): 166–171

CO-Releasing Molecule (CORM-2) in the Regulation of Ca2+-Dependent K+-Permeability of Erythrocyte

Beschasnyi S., Hasiuk O.

In recent decades, the scientists have discovered the existence of a new class of biologically active substances – gaseous intermediaries, which perform a signaling function in the cells and with a high specificity are involved in intercellular and intracellular communication. A special place is occupied by carbon monoxide. We conducted an experimental study of the effect of the donor of carbon monoxide CORM-2 on the change in the volume of red blood cells after cultivation in solutions with different osmotic forces. It is known that the change in the volume of red blood cells is controlled by Ca2+ -activated K+channels (K+(Ca2+)) or Gardos channels. To study the effect of CORM-2 on K+(Ca2+) erythrocyte channels, donor blood was used. The red blood cells were pre-washed in phosphate buffered saline with glucose. To prove the effect of CORM-2 on K+(Ca2+) channels in a parallel sample, these channels were blocked with clotrimazole, a known blocker. To clarify the activity of K+(Ca2+) channels after incubation, red blood cells were placed in the media with different osmotic strengths: 220, 320, 420, and 520 mosm. After that, the degree of light transmission was measured. The cultivation of red blood cells with different concentrations showed a dose-dependent effect of CORM-2 on the K+(Ca2+) channels of red blood cells. As a result of the studies, it was found that CORM-2 is able to block K+(Ca2+) channels. This confirms that the light transmission of the erythrocyte suspension (increase in red blood cell volume) after treatment with CORM-2 was the same as after treatment with clotrimazole. It should be noted that the effects of CORM-2 are dose-dependent. The maximum blocking effect of CORM-2 on K+(Ca2+) channels was observed at a concentration of 200 and 10 μM. At a concentration of 100 μM in a hypotonic solution of 220 mosm, the opposite effect was observed – water leakage from red blood cells (a decrease in the volume of red blood cells indicates this). This phenomenon can be explained by the effect of red blood cells on aquaporins.

Keywords: Gardos channel, CO-releasing molecule, carbon monoxide, erythrocytes

Full text: PDF (Eng) 481K

  1. Serroukh Y, Djebara S, Lelubre C, Zouaoui Boudjeltia K, Biston P, Piagnerelli M. Alterations of the erythrocyte membrane during sepsis. J Crit Care Res Practice. 2012; 2012:702956. PMID: 22675622. PMCID: PMC3363976.
  2. Faizan M, Muhammad N, Niazi KUK, Hu Y, Wang Y, Wu Y, et al. CO-releasing materials: an emphasis on therapeutic implications, as release and subsequent cytotoxicity are the part of therapy. Materials (Basel). 2019; 20: 12(10): 1643. PMID: 31137526. PMCID: PMC6566563.
  3. Kolupaev YE, Karpets YV, Beschasniy SP, Dmitriev AP. Gasotransmitters and their role in adaptive reactions of plant cells. Cytol Genet. 2019; 53: 392.
  4. Wang R, Ed. Signal Transduction and the Gasotransmitters: NO, CO, and H2S in Biology and Medicine. Humana Press; 2010. 378 p.
  5. Olas B. Carbon monoxide is not always a poison gas for human organism: Physiological Q1 and pharmacological features of CO. Chem Biol Interact. 2014; 222: 37-43.
  6. Coburn RF, Blakemore WS, Forester RE. Endogenous carbon monoxide production in man. J Clin Invest. 1963 42: 1172–8.
  7. Piantadosi CA. Carbon monoxide, reactive oxygen signaling, and oxidative stress. Free Radic Biol Med. 2008; 45: 562–9.
  8. Koch CA, Khalpey ZI, Platt JL. Accommodation: preventing injury in transplantation and disease. J Immunol. 2004; 172 (9): 5143-8. PMID: 15100249.
  9. Kapetanaki SM, Burton MJ, Basran J, Uragami C, Moody PCE, Mitcheson JS, et al. A mechanism for CO regulation of ion channels. Nat Commun. 2018; 9(1): 3354. PMID: 30120224. PMCID: PMC6097995.
  10. Motterlini R, Foresti R. Biological signaling by carbon monoxide and carbon monoxide-releasing molecules. Am J Physiol Cell Physiol. 2017; 312(3): C302-13.
  11. Magierowska K, Korbut E, Hubalewska-Mazgaj M, Surmiak M, Chmura A, Bakalarz D, et al. Oxidative gastric mucosal damage induced by ischemia/reperfusion and the mechanisms of its prevention by carbon monoxide-releasing tricarbonyldichlororuthenium (II) dimer. Free RadicBiol Med. 2019; 145: 198-208. PMID: 31568823.
  12. Motterlini R, Mann BE, Johnson TR, Clark JE, Foresti R, Green CJ. Bioactivity and pharmacological actions of carbon monoxide-releasing molecules. Curr Pharm Des. 2003; 9(30): 2525–39. PMID: 14529551.
  13. Liu Y, Wang X, Xu X, Qin W, Sun B. Protective effects of carbon monoxide releasing molecule-2 on pancreatic function in septic mice. Mol Med Rep. 2019; 19(5): 3449-58. PMID: 30896839. PMCID: PMC6470989.
  14. Qureshi OS, Zeb A, Akram M, Kim MS, Kang JH, Kim HS, et al. Enhanced acute anti-inflammatory effects of CORM-2-loaded nanoparticles via sustained carbon monoxide delivery. Eur J Pharm Biopharm. 2016; 108: 187-95. PMID: 27634645.
  15. Lin CC, Hsiao LD, Cho RL, Yang CM. Carbon monoxide releasing molecule-2-upregulated ROS-dependent heme oxygenase-1 axis suppresses lipopolysaccharide-induced airway inflammation. Int J Mol Sci. 2019; 20(13): 3157.
  16. Johnson TE, Wells RJ, Bell A, Nielsen VG, Olver CS. Carbon monoxide releasing molecule enhances coagulation and decreases fibrinolysis in canine plasma exposed to Crotalusviridis venom in vitro and in vivo. Basic Clin Pharmacol Toxicol. 2019; 125(4): 328-36. PMID: 31059181.
  17. Bor-Kucukatay M, Wenby RB, Meiselman HJ, Baskurt OK. Effects of nitric oxide on red blood cell deformability. Amer J Physiol. 2005; 284: 1577–84.
  18. Trubacheva OA, Kremeno SV, Petrova IV, et al. Participation of reactive oxygen species in regulation of Са2+-activated К+ channels of erythrocytes. Bulletin of Siberian Medicine. 2009; 8(2): 56-60. [Russian]
  19. Lang PA, Kaiser S, Myssina S, Wieder T, Lang F, Huber SM. Role of Ca2+ activated K+ channels in human erythrocyte apoptosis. Am J Physiol Cell Physiol. 2003; 285(6): C1553–60. PMID: 14600080.