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 of 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 - researcher, PhD

Dr. Olena Iegorova - researcher, MD, PhD

Dr. Viacheslav Kulyk - researcher, PhD

Dr. Oksana Rybachuk - researcher, PhD

Dr. Dariia Dryn - researcher, PhD

Dr. Mariia Melnyk - researcher, PhD

Tetiana Volkova - researcher

Andrii Buta - researcher

Liudmila Nikolaienko - junior researcher

Olha Zapukhliak - junior researcher

Volodymyr Khmyz - junior researcher

Yurii Tkachenko - junior researcher

Artur Romanov - junior researcher

Oleksii Lunko - junior researcher

Olesia Lunko - junior researcher

Ruslan Bohovyk - junior researcher

Mykhailo Fedoriuk - junior researcher

Olena Kotyk - junior researcher

Artem Venhreniuk

PhD students

Sofiia Demchenko

Mariia Stefanenko

Marharyta Semenikhina

Oksana Nikolaienko

Pavlo Novikov

Iuliia Nesterenko

Publications

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