Department of Cellular Membranology

Our research

Our Department research is focused on the role of membrane proteins, mainly ion channels and metabotropic receptors, in the functioning of single neurons, neural networks, and the whole organs. The current research topics of the Department are:

  • biophysical and pharmacological properties of ion channels and receptors of cellular membranes (plasmalemma and nuclear envelope);
  • molecular mechanisms of epilepsy and epileptogenesis and pharmacological agents with antiseizure properties;
  • role of membrane receptors and ion channels in synaptic plasticity, learning, integral activity of nervous system and behavior;
  • peripheral and central mechanisms of pain and possible ways of its correction;
  • using stem cells for the treatment of neurological disorders (Alzheimer’s, Parkinson’s disease, epilepsy, and ischemic stroke) and
    traumatic injuries of the spinal cord.

Methods

Highly qualified Departments staff has strong expertise in virtually all electrophysiological techniques, various disease models and cell/tissue cultural techniques allowing studying physiological functions and some pathologies from molecular to system levels including:

  • pharmacological patch-clamp studies of different ion channels in acutely isolated cells (pyramidal neurons from hippocampus, cortex, and hypothalamus; Purkinje and granule neurons from cerebellum; spinal dorsal horn neurons; primary sensory neurons; glial cells), cultured cells (the same as above; cancer cell lines) and heterologous expression systems (HEK293, CHO, and PC-12 lines);
  • registration of electrical activity of single neurons, local field potentials, EEG in freely behaving animals;
  • isolation and cultivation of stem cells and tissue engineering;
  • electrophysiological studies of primary nociception ex vivo and in vivo;
  • seizure-like activity in acute isolated and cultured brain slices in various models of epilepsy as well as intracranial EEG in various in vivo models of epilepsy;
  • a wide range of behavioral tests (open field, different mazes, Morris water maze, etc) that allow us to study general locomotor activity, anxiety and depression-like behavior, learning and memory, social behavior, etc.

Collage (clockwise): ”The effect of ASIC1a inhibition on hippocampal LTP (Buta A et. al, J. Med. Chem. 2015); patch-clamp technique (V. Kulyk); confocal microscopy of neural stem cell culture and neurospheres – astrocytes are red, neurons blue (O. Rybachuk); brain structures’ LFPs in freely moving rat and it’s spectrogram (R. Bohovyk); meeting colleagues at FENS Forum (A. Cherninskyi and E. Knapska); making artificial cerebrospinal fluid (O. Iegorova); central — specimens’ microscopy (M. Fedoriuk).”

Members

  • Prof. Oleg Krishtal – the head of department, PhD, DSc, Professor, Member of Academia Europaea, Full Member of the National Academy of Sciences of Ukraine
  • Dr. Oleksandr Maximyuk – leading researcher, PhD
  • Dr. Maksim Storozhuk – leading researcher, PhD, Dsc
  • Dr. Dmytro Isaev – leading researcher, PhD
  • Dr. Ihor Chizhmakov – senior researcher, PhD
  • Dr. Andrii Cherninskyi – senior researcher, PhD
  • Dr. Anna Kotliarova – senior researcher, PhD
  • Dr. Alina Savotchenko – senior researcher, PhD
  • Dr. Oksana Rybachuk – senior researcher, PhD
  • Dr. Olena Iegorova – researcher, MD, PhD
  • Dr. Viacheslav Kulyk – researcher, PhD
  • Dr. Dariia Dryn – researcher, PhD
  • Dr. Mariia Melnyk – researcher, PhD
  • Dr. Nataliia Novosiolova – researcher, PhD
  • Dr. Marharyta Semenikhina – junior researcher, PhD
  • Dr. Olena Kotyk – junior researcher, PhD
  • Dr. Artur Romanov – junior researcher, PhD
  • Dr. Olesia Lunko – junior researcher, PhD
  • Dr. Ruslan Bohovyk – junior researcher, PhD
  • Dr. Mykhailo Fedoriuk – junior researcher, PhD
  • Dr. Olha Zapukhliak – junior researcher, PhD
  • Dr. Oleksandr Sudakov – leading engineer, PhD
  • Tetiana Volkova – researcher
  • Andrii Buta – researcher
  • Liudmila Nikolaienko – junior researcher
  • Volodymyr Khmyz – junior researcher
  • Yurii Tkachenko – junior researcher
  • Oleksii Lunko – junior researcher
  • Artem Venhreniuk – engineer
  • Mariia Stefanenko – engineer
  • Oksana Nikolaienko – engineer
  • Iuliia Nesterenko – engineer
  • Ahmad Dzhuma – engineer

PhD students

  • Sofiia Demchenko
  • Mariia Stefanenko
  • Oksana Nikolaienko
  • Pavlo Novikov
  • Iuliia Nesterenko
  • Bohdan Kushch

Publications

Zapukhliak O, Netsyk O, Romanov A, Maximyuk O, Oz M, Holmes GL, Krishtal O, Isaev D Mecamylamine inhibits seizure-like activity in CA1-CA3 hippocampus through antagonism to nicotinic receptors // PLOS ONE, 2021, Vol. 16, Issue 3, Article Number e0240074 DOI 10.1371/journal.pone.0240074

Melnick I, Krishtal OA, Colmers WF Integration of energy homeostasis and stress by parvocellular neurons in rat hypothalamic paraventricular nucleus // JOURNAL OF PHYSIOLOGY-LONDON, 2020, Vol. 598, Issue 5, P. 1073-1092 DOI 10.1113/JP279387

Lai K, Song XL, Shi HS, Qi X, Li CY, Fang J, Wang F, Maximyuk O, Krishtal O, Xu TL Bilirubin enhances the activity of ASIC channels to exacerbate neurotoxicity in neonatal hyperbilirubinemia in mice // SCIENCE TRANSLATIONAL MEDICINE, 2000, Volume 12, Issue 530, Article Number eaax1337 DOI10.1126/scitranslmed.aax1337

Melnyk MI, Dryn DO, Al Kury LT, Dziuba DO, Zholos AV 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, Volume 11, Article  Number 594882 DOI 10.3389/fphar.2020.594882


Kulyk VB, Chizhmakov IV, Iegorova OV, Volkova TM, Kharytonenko GI, Drozd OO, Krishtal OA Ganglion-Specific Sensitivity of P2X3 Receptors to Leu-Enkephalin // NEUROPHYSIOLOGY, 2020, Volume 52, Issue 3, P. 186-191 DOI 10.1007/s11062-020-09869-y

Li, HS; Su, XY; Song, XL; Qi, X; Li, Y; Wang, RQ; Maximyuk, O; Krishtal, O; Wang, TT; Fang, HQ; Liao, LJ; Cao, H; Zhang, YQ; Zhu, MX; Liu, MG; Xu, TL Protein Kinase C Lambda Mediates Acid-Sensing Ion Channel 1a-Dependent Cortical Synaptic Plasticity and Pain Hypersensitivity // JOURNAL OF NEUROSCIENCE, 39 (29), 2019, P. 5773-5793 DOI: 10.1523/JNEUROSCI.0213-19.2019

Rybachuk, O; Kopach, O; Pivneva, T; Kyryk, V Isolation of Neural Stem Cells from the Embryonic Mouse Hippocampus for in vitro Growth or Engraftment into a Host Tissue // BIO-PROTOCOL, 9 (4), 2019, Article Number: e3165 DOI: 10.21769/BioProtoc.3165

Semenikhina, M; Bogovyk, R; Fedoriuk, M; Nikolaienko, O; Al Kury, LT; Savotchenko, M; Krishtal, O; Isaeva, E Inhibition of protease-activated receptor 1 ameliorates behavioral deficits and restores hippocampal synaptic plasticity in a rat model of status epilepticus // NEUROSCIENCE LETTERS, 692, 2019, P. 64-68 DOI: 10.1016/j.neulet.2018.10.058

Kopach, O; Rybachuk, O; Krotov, V; Kyryk, V; Voitenko, N; Pivneva, T Maturation of neural stem cells and integration into hippocampal circuits – a functional study in an in situ model of cerebral ischemia // JOURNAL OF CELL SCIENCE, 131 (4), 2018, pii: jcs210989 DOI: 10.1242/jcs.210989

Luo, JL; Qian, AH; Oetjen, LK; Yu, WH; Yang, P; Feng, J; Xie, ZL; Liu, SB; Yin, SJ; Dryn, D; Cheng, JZ; Riehl, TE; Zholos, AV; Stenson, WF; Kim, BS; Hu, HZ TRPV4 Channel Signaling in Macrophages Promotes Gastrointestinal Motility via Direct Effects on Smooth Muscle Cells // IMMUNITY, 49 (1), 2018, P. 107-119 DOI: 10.1016/j.immuni.2018.04.021

Kononenko, O; Galatenko, V; Andersson, M; Bazov, I; Watanabe, H; Zhou, XW; Iatsyshyna, A; Mityakina, I; Yakovleva, T; Sarkisyan, D; Ponomarev, I; Krishtal, O; Marklund, N; Tonevitsky, A; Adkins, DL; Bakalkin, G Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits // FASEB JOURNAL, 31 (5), 2017, P. 1953-1963 DOI: 10.1096/fj.201601039R

Kononenko, O; Bazov, I; Watanabe, H; Gerashchenko, G; Dyachok, O; Verbeek, DS; Alkass, K; Druid, H; Andersson, M; Mulder, J; Svenningsen, AF; Rajkowska, G; Stockmeier, CA; Krishtal, O; Yakovleva, T; Bakalkin, G Opioid precursor protein isoform is targeted to the cell nuclei in the human brain // BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1861 (2), 2017, P. 246-255 DOI: 10.1016/j.bbagen.2016.11.002

Feng, J; Yang, P; Mack, MR; Dryn, D; Luo, JL; Gong, X; Liu, SB; Oetjen, LK; Zholos, AV; Mei, ZN; Yin, SJ; Kim, BS; Hu, HZ Sensory TRP channels contribute differentially to skin inflammation and persistent itch // NATURE COMMUNICATIONS, 8, 2017, Article Number: 980 DOI: 10.1038/s41467-017-01056-8

Storozhuk, M; Kondratskaya, E; Nikolaenko, L; Krishtal, O A modulatory role of ASICs on GABAergic synapses in rat hippocampal cell cultures // MOLECULAR BRAIN, 9, 2016, Article Number: 90 DOI: 10.1186/s13041-016-0269-4

Liu, MG; Li, HS; Li, WG; Wu, YJ; Deng, SN; Huang, C; Maximyuk, O; Sukach, V; Krishtal, O; Zhu, MX; Xu, TL Acid-sensing ion channel 1a contributes to hippocampal LTP inducibility through multiple mechanisms // SCIENTIFIC REPORTS, 6, 2016, Article Number: 23350 DOI: 10.1038/srep23350

Tesoriero, C; Codita, A; Zhang, MD; Cherninsky, A; Karlsson, H; Grassi-Zucconi, G; Bertini, G; Harkany, T; Ljungberg, K; Liljestrom, P; Hokfelt, TGM; Bentivoglio, M; Kristensson, K H1N1 influenza virus induces narcolepsy-like sleep disruption and targets sleep-wake regulatory neurons in mice // Proceedings Of The National Academy Of Sciences Of The United States Of America, 113 (3), 2016, E368-E377 DOI: 10.1073/pnas.1521463112

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., Zholos, A Bradding P., Ennis M., 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 133 (3), 2014, 704-712 DOI: 10.1016/j.jaci.2013.09.016

Krishtal O Receptor for protons: First observations on Acid Sensing Ion Channels // NEUROPHARMACOLOGY, 94, 2015, P. 4-8 DOI: 10.1016/j.neuropharm.2014.12.014

Ievglevskyi O, Isaev D, Netsyk O, Romanov A, Fedoriuk M, Maximyuk O, Isaeva E, Akaike N, Krishtal O Acid-sensing ion channels regulate spontaneous inhibitory activity in the hippocampus: possible implications for epilepsy // The Royal Society Phil. Trans. R. Soc. B, 2016, 371(1700). pii: 20150431 DOI: 10.1098/rstb.2015.0431

Buta A, Maximyuk O, Kovalskyy D, Sukach V, Vovk M, Isaev D, Ievglevskyi O, Isaeva E, Savotchenko A, Krishtal O Novel potent orthosteric antagonist of ASIC1a prevents NMDAR-dependent LTP induction // J Med Chem. 2015 Jun 11;58(11):4449-61 DOI: 10.1021/jm5017329