Biophysical properties and functional roles of receptors and ion channels

Previous and Current Research

Prof. Zholos has long-standing interests in ion channel research and over 30 years of hands-on and supervisory experience in this area. This research employs patch-clamp recording techniques in combination with Ca²⁺ imaging and molecular biology approaches. It includes investigation of single ion channel mechanisms and the roles of multiple ligands in the regulation of novel TRP channels, as well as voltage-gated and receptor-operated channels in excitable and non-excitable cells.

Recent research highlights include identification of:

• receptor-operated TRPC4 channels as the main molecular component of the muscarinic cation current in small intestine, which underlines cholinergic-excitation-contraction coupling in the gut;
• molecular mechanisms of TRPC4 regulation and signalling;
• enhanced expression and function of the heat and capsaicin receptor TRPV1 in severe bronchial asthma;
• single-channel mechanisms of the cold and menthol receptor TRPM8 gating, as well as TRPM8 function in the vasculature;
• biophysical and pharmacological characterisation of volume-regulated anion channels as an alternative pathway for chloride secretion in cystic fibrosis respiratory epithelial cells;
• nanostructured materials (e.g. C₆₀ fullerenes, carbon nanotubes) as novel modulators of BK_Ca and TRPC4 channels activity;
• inhibitory action of general anaesthetics (isoflurane and ketamine) on the muscarinic cation current and carbachol-induced gastrointestinal smooth muscle contractions.

This research was funded by Ministry of Education and Science of Ukraine, Department of Targeted Education of Taras Shevchenko National University of Kyiv at the National Academy of Sciences of Ukraine, The Wellcome Trust (UK), British Heart Foundation (UK), National Institutes of Health (USA), NI Chest Heart & Stroke (Northern Ireland), Biotechnology and Biological Sciences Research Council (UK), The Royal Society (UK), The Physiological Society (UK), Mext (Japan), DEL (UK).

We have recently completed research project on ““Molecular and cellular mechanisms of TRP channelopathies” (2019-2021) and we are currently investigating “Transport of ions and oxalates as a key factor in chronic kidney disease and associated pathologies” (2022-2024).  Both projects have been funded by the Ministry of Education and Science of Ukraine. This research involves collaborations with clinical researches and institutes of the Academy of Sciences of Ukraine and the National Academy of Medical Sciences of Ukraine.

Future Projects and Goals

Ongoing research aims to develop and characterise novel activators and inhibitors of large-conductance Ca²⁺-activated potassium channels (maxi-K channels) and receptor operated TRP channels, which can be useful for the treatment of many disease states associated with either hyperactivity or reduced contractility of visceral and vascular smooth muscles, including pulmonary hypertension, irritable bowel syndrome, Parkinson’s disease, inflammatory colitis, disorders of uterus contractility, as well as chronic kidney disease.

Patch-clamp recording of Maxi-K channel activation by green laser-induced plasmon resonance (A) in an isolated arterial smooth muscle myocyte (B). In the cell-attached configuration, laser-illuminated AuNCs activate single Maxi-K channels in rat pulmonary artery myocytes in a remote manner (C).

Methodological and Technical Expertise

• animal models of human disease, such as diabetes, Parkinson’s disease, and inflammatory colitis;
  
• cell isolation techniques;
  
• tensiometry for in vitro and in vivo recording of muscle contractile responses;
  
• all variants of patch-clamp techniques (whole-cell and single channel recordings);
  
• calcium imaging using CCD camera and confocal microscopy;
  
• Ussing chamber for the investigation of ion transport and epithelial barrier function;
  
• immunocyto/histochemistry, PCR and qRT-PCR;
  
• data analysis using pClamp and MicroCal Origin software, custom programming:
  

http://www.originlab.com/fileExchange/details.aspx?fid=315

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Membership of Editorial Boards:

Frontiers in Pharmacology (Scopus, WoS): Review Editor of Frontiers in Integrative and Regenerative Pharmacology - since 2010

International Journal of Physiology and Pathophysiology (Scopus) - since 2010

Medicinal Chemistry (Scopus, WoS) – (2018-2021)

Current Molecular Pharmacology (Scopus, WoS) – (2018-2021)

Current Neuropharmacology (Scopus, WoS) – (2018-2021)

Frontiers in Cellular Neuroscience (Scopus, WoS) – since 2020

Research team members                            Research profile

Prof. G.M. Tolstanova, DSc                            Scopus

Dr T.V. Dovbynchuk, PhD                               Scopus

Dr O.F. Moroz, PhD                                        Scopus

Dr D.M. Nozdrenko, PhD                                Scopus

Dr V.M. Soroca, PhD                                      Scopus

Dr M.I. Melnyk M.I., PhD                                Scopus

Dr D.O. Dryn, PhD                                         Scopus

V. O. Stetska, PhD student                                      

O.G. Basovska, PhD student      

N.V. Levitsky, PhD student         

Selected Publications

Research papers:

Bidaux G., Beck B., Zholos A., Gordienko D., Lemonnier L., Flourakis M., Roudbaraki M., Borowiec A.-S., Fernández J., Delcourt P., Lepage G., Shuba Ya., Skryma R., Prevarskaya N.

Regulation of activity of Transient Receptor Potential melastatin 8 (TRPM8) channel by its short isoforms.

Journal of Biological Chemistry, 2012, 287, 2948-2962 (IF=4.258)

Fernández J.A., Skryma R., Bidaux G., Magleby K.L., Scholfield C.N., McGeown J.G., Prevarskaya N., Zholos A.V.

Short isoforms of the cold receptor TRPM8 inhibit channel gating by mimicking heat action rather than chemical inhibitors.

Journal of Biological Chemistry, 2012, 287, 2963-2970 (IF=4.258)

de Courcey F., Zholos A.V., Atherton-Watson H., Williams M.T., Canning P., Danahay H.L., Elborn J.S., Ennis M.

Development of primary human nasal epithelial cell cultures for the study of cystic fibrosis pathophysiology.

American Journal of Physiology – Cell Physiology, 2012, 303, C1173-1179 (IF=3.395)

McGarvey L.P., Butler C.A., Stokesberry S., Polley L., McQuaid S., Abdullah H., Ashraf S.,  McGahon M.K., Curtis T.M., Arron J., Choy D., Warke T.J., Bradding P., Ennis M., Zholos A., Costello R., Heaney L.G.

Increased expression of bronchial epithelial transient receptor 1 potential vanilloid 1 channels in severe asthma.

Journal of Allergy and Clinical Immunology, 2014, 133, 704-712 (IF=12.485)

Stott J.B., deCourcey F., Ennis M., Zholos A.V.

Functional and pharmacological characterization of volume-regulated anion channels in human normal and cystic fibrosis bronchial and nasal epithelial cells.

European Journal of Pharmacology, 2014, 740, 183-191 (IF=2.73)

Soloviev A., Zholos A., Ivanova I., Novokhatska T., Tishkin S.,  Raevska A., Stroyuk A, Yefanov V.

Plasmonic gold nanoparticles possess the ability to open potassium channels in rat thoracic aorta smooth muscles in a remote control manner.

Vascular Pharmacology, 2015, 72, 190-196 (IF=2.500)

Bidaux G., Sgobba M., Lemonnier L., Borowiec A.S., Noyer L., Jovonovic S.,  Zholos A.V., Haider S.

Functional and modelling studies of the transmembrane region of the TRPM8 channel.

Biophysical Journal, 2015, 109 (9), 1840-1851 (IF=3.632)

McGahon M.K., Fernández J.A., Dash D.P., McKee J., Simpson D.A., Zholos A.V., McGeown J.G., Curtis T.M.

TRPV2 channels contribute to stretch-activated cation currents and myogenic constriction in retinal arterioles.

Investigative Ophthalmology & Visual Science, 2016, 57 (13), 5637-5647 (IF=3.427)

Melanaphy D., Johnson C.D., Kustov M.V., Watson C.A., Borysova L., Burdyga T.V., Zholos A.V.

Ion channel mechanisms of rat tail artery contraction-relaxation by menthol involving, respectively, TRPM8 activation and L-type Ca²⁺ channel inhibition.

American Journal of Physiology – Heart & Circulatory Physiology, 2016, 311 (6), H1416-H1430 (IF=3.324)

Feng J., Yang P., Mack M.R., Dryn D., Luo J., Gong X., Liu S., Oetjen L.K., Zholos A.V., Mei Z., Yin S., Kim B.S., Hu H. (2017).

Sensory TRP channels contribute differentially to skin inflammation and persistent itch.

Nature Communications, 2017, 8 (1), 980 (1-12) (IF= 11.878)

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.

European Journal of Pharmacology, 2018, 820, 39-44 (IF=3.170)

Dryn D.O., Melnyk M.I., Al Kury L.T., Prylutskyy Yu.I., Ritter U., Zholos A.V. (2018).

C₆₀ fullerenes disrupt cellular signalling leading to TRPC4 and TRPC6 channels opening by the activation of muscarinic receptors and G-proteins in small intestinal smooth muscles.

Cellular Signalling, 2018, 43, 40-46 (IF=3.937)

Luo J., Qian A., Oetjen L.K., Yu W., Yang P., Feng J., Xie Z., Liu S., Yin S., Dryn D., Cheng J., Riehl T.E., Zholos A.V., Stenson W.F., Kim B.S., Hu H. (2018).

TRPV4 channel signaling in macrophages promotes gastrointestinal motility via direct effects on smooth muscle cells.

Immunity, 2018, 49(1), 107-119.e4 (IF= 19.734)

Melnyk M.I., Ivanova I.V., Dryn D.O., Prylutskyy Y.I., Hurmach V.V., Platonov M., Al Kury L.T., Ritter U., Soloviev A.I., Zholos A.V.

C₆₀ fullerenes selectively inhibit BK_Ca but not K_V channels in pulmonary artery smooth muscle cells.

Nanomedicine: Nanotechnology, Biology and Medicine, 2019, 19, 1-11 (IF=5.57)

Melnyk M.I., Dryn D.O., Al Kury L.T., Dziuba D.O., Zholos A.V.

Suppression of mI_CAT in mouse small intestinal myocytes by general anaesthetic ketamine and its recovery by TRPC4 agonist (-)-englerin A.

Frontiers in Pharmacology, 2020, 11, 1-12 (IF=4.4)

Ivanova I.V., Melnyk M.I., Dryn D.O., Prokhorov V.V., Zholos A.V., Soloviev A.I.

Electrophysiological characterization of the activating action of a novel liposomal nitric oxide carrier on Maxi-K channels in pulmonary artery smooth muscle cells.

Journal of Liposome Research, 2021 Jan 8;1-10 (IF=2.455)

Al Kury L.T., Papandreou D., Hurmach V.H., Dryn D.O., Melnyk M.I., Platonov M.O., Prylutskyy Y.I., Ritter U., Scharff  P., Zholos A.V.

Single-walled carbon nanotubes inhibit TRPC4-mediated muscarinic cation current in mouse ileal myocytes.

Nanomaterials 2021, 11(12), 3410 (IF=5.346)

Nozdrenko D., Matvienko T., Vygovska O., Soroca V., Bogutska K., Zholos A., Scharff P., Ritter U., Prylutskyy Yu.

Post-traumatic recovery of muscle soleus in rats is improved via synergistic effect of C₆₀ fullerene and TRPM8 agonist menthol.

Applied Nanoscience, 2022, 12(3), 467-478. (IF=3.198)

Invited reviews and book chapters:

Zholos A.V., Curtis T.M.

TRP channels in vascular disorders.

Current Topics in Medicinal Chemistry, 2013, 13, 295-309 (IF=3.402)

Zholos A.V.

TRPC5.

In “Mammalian Transient Receptor Potential (TRP) Cation Channels”, Handbook of Experimental Pharmacology, Eds. B. Nilius V. Flockerzi, Springer-Verlag Berlin Heidelberg, 2014, 222, 129-156.

Zholos A.V., McGarvey L., Ennis M.

TRPs in respiratory disorders: opportunities beyond TRPA1.

In: “TRP Channels as Therapeutic Targets: From Basic Science to Clinical Use”. Editor A. Szallasi. Elsevier, Academic Press, 2015, 536 pp., Chapter 26, 483-500.

Zholos A.V.

TRP channels in respiratory pathophysiology: the role of oxidative, chemical irritant and temperature stimuli.

Current Neuropharmacology 2015, 13 (2), 279-291 (IF=3.753)

Storozhuk M.V., Zholos A.V.

TRP channels as novel targets for endogenous ligands: focus on endocannabinoids and nociceptive signalling.

Current Neuropharmacology, 2018, 16 (2), 137-150 (IF=4.568)

Moroz O., Zholos A.

Uterine myocytes: development, structure and function.

In: “Advances in Medicine and Biology”, Editor L.V. Berhardt, Nova Science Publishers, Inc., 2019, vol. 148, Chapter 2, 27-96.

Storozhuk M.V., Moroz O.F., Zholos A.V.

Multifunctional TRPV1 ion channels in physiology and pathology with focus on the brain, vasculature, and some visceral systems.

BioMed Research International, 2019, v. 2019, 1-12. (IF=2.583)

Zholos A.V., Moroz O.F., Storozhuk M.V.

Curcuminoids and novel opportunities for the treatment of Alzheimer's disease: which molecules are actually effective?

Current Molecular Pharmacology 2019, 12 (1), 12-26. (IF=3.339)

TRiPs across epithelial and endothelial barriers in health and disease.

Editors A.V. Zholos, G.M. Tolstanova, Nova Science Publishers, New York, 2021, 257 pp. ISBN: 978-1-68507-020-5.

Research profiles:

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Contacts

Phone: +38(0 44) 431 04 03