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Laboratory of Cellular Neurophysiology

Laboratory of Cellular Neurophysiology

Research of the Laboratory of Cellular Neurophysiology focuses on the function and pharmacology of ionotropic receptors (ligand-activated ion channels), specifically ionotropic glutamate receptors (iGluRs) and transient receptor potential (TRP) channels.  iGluRs mediate the majority of excitatory signaling in the central nervous system, are essential for normal brain development and function, and their dysfunction leads to serious neurological and psychiatric disorders, including many forms of neurodegeneration.  TRP channels are present in both the peripheral and the central nervous system, and they play a fundamental role in the detection and transmission of painful stimuli and participate in signaling associated with chronic inflammation.

The goal of our research is to better characterize the relationship between ionotropic receptor structure and function, to identify molecular mechanisms of ionotropic receptor modulation by different chemical compounds or physical variables, and to describe the consequences of mutations of human ionotropic receptors for the function of synapses, neurons and neuronal networks.  Obtained results deepen our basic understanding of the mechanisms of ionotropic receptor function, and inform the development of novel receptor modulators with therapeutic potential in the treatment of neurodevelopmental and neurodegenerative disorders.

History of the Laboratory    History of the Laboratory II

Methods

Alumni List

Projects

Glutamate receptor research

Glutamate is the primary excitatory neurotransmitter in the central nervous system. NMDA receptors (NMDARs) are ionotropic glutamate receptors that detect glutamate in the context of ongoing circuit activity. NMDAR activation requires the binding of glutamate as an agonist and glycine as a co-agonist, together with sufficient membrane depolarization to relieve the voltage-dependent channel block by extracellular Mg2+. In addition, NMDAR function is tightly regulated by a number of endogenous modulators. Upon activation, the NMDAR forms a cation channel highly permeable to Ca2+, a second messenger that coordinates downstream signalling leading to activity-dependent changes in synaptic strength. NMDARs are therefore critical for the development of neural circuits and for their ability to process information. More

TRP channel research

We investigate molecular mechanisms of nociception and thermosensation by focusing on thermosensitive transient receptor potential (TRP) ion channels. These channels are specifically expressed in primary nociceptive neurons and work in concert to detect potentially damaging stimuli and transduce them into pain signalling.   The goal of our research is to understand the physiological or pathophysiological significance of specific subclasses of TRP ion channels involved in the detection of noxious thermal, mechanical and chemical stimuli, through deciphering molecular and biophysical principles of their operational features. We use electrophysiological and microfluorometric techniques, mainly patch-clamp recording at whole-cell and single-channel levels. For a more detailed understanding of TRP ion channel activation mechanisms we also use biochemistry and molecular biology combined with molecular modelling. More

Publications

Kolcheva; Marharyta - Ladislav; M. - Netolický; J. - Kortus; Š. - Řeháková; K. - Hrčka Krausová; B. - Hemelíková; K. - Misiachna; A. - Kádková; A. - Klíma; Martin - Chalupská; Dominika - Horák; M. The pathogenic N650K variant in the GluN1 subunit regulates the trafficking; conductance; and pharmacological properties of NMDA receptors . Neuropharmacology. 2023; 222(1 January)); 109297 . IF = 4.7 [ASEP] [ doi ]
Abramová; Vera - Alvarado; Vanessa Leal - Hill; M. - Smejkalová; Tereza - Malý; Michal - Valeš; Karel - Dittert; Ivan - Božíková; Paulina - Kysilov; Bohdan - Hrčka Krausová; Barbora - Vyklický; Vojtěch - Balík; Aleš - Fili; Klevinda - Kořínek; Miloslav - Chodounská; Hana - Kudová; Eva - Číž; D. - Martinovič; J. - Bartůněk; Petr - Vyklický ml.; Ladislav . Effects of Pregnanolone Glutamate and Its Metabolites on GABAA and NMDA Receptors and Zebrafish Behavior . ACS Chemical Neuroscience. 2023; 14(10); 1870-1883 . IF = 5.0 [ASEP] [ doi ]
Zímová; Lucie - Ptáková; Alexandra - Mitro; Michal - Krůšek; Jan - Vlachová; Viktorie . Activity dependent inhibition of TRPC1/4/5 channels by duloxetine involves voltage sensor-like domain . Biomedicine & Pharmacotherapy. 2022; 152(August)); 113262 . IF = 7.5 [ASEP] [ doi ]
Zhang; L. - Simonsen; Ch. - Zímová; Lucie - Wang; K. - Moparthi; L. - Gaudet; R. - Ekoff; M. - Nilsson; G. - Hellmich; U. A. - Vlachová; Viktorie - Gourdon; P. - Zygmunt; P. M. Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function . Nature Communications. 2022; 13(1)); 7483 . IF = 16.6 [ASEP] [ doi ]
Štefková-Mazochová; K. - Danda; H. - Dehaen; W. - Jurásek; B. - Šíchová; K. - Pinterová-Leca; N. - Mazoch; V. - Hrčka Krausová; Barbora - Kysilov; Bohdan - Smejkalová; Tereza - Vyklický ml.; Ladislav - Kohout; M. - Hájková; K. - Svozil; Daniel - Horsley; R. R. - Kuchař; M. - Páleníček; T. Pharmacokinetic; pharmacodynamic; and behavioural studies of deschloroketamine in Wistar rats . British Journal of Pharmacology. 2022; 179(1); 65-83 . IF = 7.3 [ASEP] [ doi ]
Ptáková; Alexandra - Mitro; Michal - Zímová; Lucie - Vlachová; Viktorie . Cellular context determines primary characteristics of human TRPC5 as a cold-activated channel . Journal of Cellular Physiology. 2022; 237(9); 3614-3626 . IF = 5.6 [ASEP] [ doi ]
Moparthi; L. - Sinica; Viktor - Moparthi; V. K. - Kreir; M. - Vignane; T. - Filipovic; M. R. - Vlachová; Viktorie - Zygmunt; P. M. The human TRPA1 intrinsic cold and heat sensitivity involves separate channel structures beyond the N-ARD domain . Nature Communications. 2022; 13(1)); 6113 . IF = 16.6 [ASEP] [ doi ]
Kysilov; Bohdan - Hrčka Krausová; Barbora - Vyklický; Vojtěch - Smejkalová; Tereza - Kořínek; Miloslav - Horák; Martin - Chodounská; Hana - Kudová; Eva - Černý; Jiří - Vyklický ml.; Ladislav . Pregnane-based steroids are novel positive NMDA receptor modulators that may compensate for the effect of loss-of-function disease-associated GRIN mutations . British Journal of Pharmacology. 2022; 179(15); 3970-3990 . IF = 7.3 [ASEP] [ doi ]
Vyklický; Vojtěch - Stanley; Ch. - Habrian; Ch. - Isacoff; E. Y. Conformational rearrangement of the NMDA receptor amino-terminal domain during activation and allosteric modulation . Nature Communications. 2021; 12(1)); 2694 . IF = 17.694 [ASEP] [ doi ]
Smejkalová; Tereza - Kořínek; Miloslav - Krůšek; Jan - Hrčka Krausová; Barbora - Candelas Serra; Miriam - Hajduković; Dragana - Kudová; Eva - Chodounská; Hana - Vyklický ml.; Ladislav . Endogenous neurosteroids pregnanolone and pregnanolone sulfate potentiate presynaptic glutamate release through distinct mechanisms . British Journal of Pharmacology. 2021; 178(19); 3888-3904 . IF = 9.473 [ASEP] [ doi ]
Sinica; Viktor - Vlachová; Viktorie . Transient receptor potential ankyrin 1 channel: an evolutionarily tuned thermosensor . Physiological Research. 2021; 70(3); 363-381 . IF = 2.139 [ASEP] [ doi ]
Nadezhdin; K. D. - Neuberger; A. - Trofimov; Yu. A. - Krylov; N. A. - Sinica; Viktor - Kupko; N. - Vlachová; Viktorie - Zakharian; E. - Efremov; R. G. - Sobolevsky; A. I. Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel . Nature Structural & Molecular Biology. 2021; 28(7); 564-572 . IF = 18.361 [ASEP] [ doi ]
Míková; H. - Kuchtiak; Viktor - Svobodová; Irena - Spišská; V. - Pačesová; D. - Balík; Aleš - Bendová; Z. Circadian Regulation of GluA2 mRNA Processing in the Rat Suprachiasmatic Nucleus and Other Brain Structures . Molecular Neurobiology. 2021; 58(1); 439-449 . IF = 5.686 [ASEP] [ doi ]
Konečný; J. - Misiachna; Anna - Hrabinová; M. - Pulkrábková; L. - Benková; M. - Prchal; L. - Kučera; T. - Kobrlová; T. - Finger; V. - Kolcheva; Marharyta - Kortus; Štěpán - Jun; D. - Valko; M. - Horák; Martin - Soukup; O. - Korábečný; J. Pursuing the Complexity of Alzheimer's Disease: Discovery of Fluoren-9-Amines as Selective Butyrylcholinesterase Inhibitors and N-Methyl-d-Aspartate Receptor Antagonists . Biomolecules. 2021; 11(1)); 3 . IF = 6.064 [ASEP] [ doi ]
Kolcheva; Marharyta - Kortus; Š. - Hrčka Krausová; B. - Baráčková; P. - Misiachna; A. - Danačíková; Šárka - Kaniaková; M. - Hemelíková; K. - Hotovec; M. - Řeháková; K. - Horák; M. Specific pathogenic mutations in the M3 domain of the GluN1 subunit regulate the surface delivery and pharmacological sensitivity of NMDA receptors . Neuropharmacology. 2021; 189(15 May)); 108528 . IF = 5.273 [ASEP] [ doi ]
Kaniaková; Martina - Korábečný; J. - Holubová; Kristína - Kletečková; Lenka - Chvojková; Markéta - Hakenová; K. - Prchal; L. - Novák; M. - Doležal; R. - Hepnarová; V. - Svobodová; B. - Kučera; T. - Lichnerová; Katarina - Krausová; B. - Horák; Martin - Valeš; Karel - Soukup; O. 7-phenoxytacrine is a dually acting drug with neuroprotective efficacy in vivo . Biochemical Pharmacology. 2021; 186(Apr)); 114460 . IF = 6.100 [ASEP] [ doi ]
Hubálková; Pavla - Ladislav; Marek - Vyklický; Vojtěch - Smejkalová; Tereza - Hrčka Krausová; Barbora - Kysilov; Bohdan - Krůšek; Jan - Naimová; Žaneta - Kořínek; Miloslav - Chodounská; Hana - Kudová; Eva - Černý; Jiří - Vyklický ml.; Ladislav . Palmitoylation Controls NMDA Receptor Function and Steroid Sensitivity . Journal of Neuroscience. 2021; 41(10); 2119-2134 . IF = 6.709 [ASEP] [ doi ]
Holubová; K. - Chvojková; M. - Hrčka Krausová; Barbora - Vyklický; Vojtěch - Kudová; Eva - Chodounská; Hana - Vyklický ml.; Ladislav - Valeš; Karel . Pitfalls of NMDA Receptor Modulation by Neuroactive Steroids. The Effect of Positive and Negative Modulation of NMDA Receptors in an Animal Model of Schizophrenia . Biomolecules. 2021; 11(7)); 1026 . IF = 6.064 [ASEP] [ doi ]
Hirschfeldová; Kateřina - Černý; Jiří - Božíková; P. - Kuchtiak; Viktor - Rausch; T. - Beneš; V. - Španiel; F. - Greguš; D. - Horáček; J. - Vyklický ml.; Ladislav - Balík; Aleš . Evidence for the Association between the Intronic Haplotypes of Ionotropic Glutamate Receptors and First-Episode Schizophrenia . Journal of Personalized Medicine. 2021; 11(12)); 1250 . IF = 3.508 [ASEP] [ doi ]
Gorecki; L. - Misiachna; Anna - Damborský; J. - Doležal; R. - Korábečný; J. - Čejková; L. - Hakenová; K. - Chvojková; M. - Zdarová Karasová; J. - Prchal; L. - Novák; M. - Kolcheva; Marharyta - Kortus; Štěpán - Valeš; K. - Horák; Martin - Soukup; O. Structure-activity relationships of dually-acting acetylcholinesterase inhibitors derived from tacrine on N-methyl-d-Aspartate receptors . European Journal of Medicinal Chemistry. 2021; 219(5 July)); 113434 . IF = 7.088 [ASEP] [ doi ]
Bernal; L. - Sotelo-Hitschfeld; P. - König; Ch. - Sinica; Viktor - Wyatt; A. - Winter; Z. - Hein; A. - Touška; Filip - Reinhardt; S. - Tragl; A. - Kusuda; R. - Wartenberg; P. - Sclaroff; A. - Pfeifer; J. D. - Ectors; F. - Dahl; A. - Freichel; M. - Vlachová; Viktorie - Brauchi; S. - Roza; C. - Boehm; U. - Clapham; D. E. - Lennerz; J. K. - Zimmermann; K. Odontoblast TRPC5 channels signal cold pain in teeth . Science Advances. 2021; 7(13)); eabf5567 . IF = 14.980 [ASEP] [ doi ]
Baluchová; Simona - Brycht; M. - Taylor; Andrew - Mortet; Vincent - Krůšek; Jan - Dittert; Ivan - Sedláková; Silvia - Klimša; Ladislav - Kopeček; Jaromír - Schwarzová-Pecková; K. Enhancing electroanalytical performance of porous boron-doped diamond electrodes by increasing thickness for dopamine detection . Analytica Chimica Acta. 2021; 1182(Oct); 1-16); 338949 . IF = 6.911 [ASEP] [ doi ]
Zímová; Lucie - Barvíková; Kristýna - Máčiková; Lucie - Vyklická; Lenka - Sinica; Viktor - Barvík; I. - Vlachová; Viktorie . Proximal C-Terminus Serves as a Signaling Hub for TRPA1 Channel Regulation via Its Interacting Molecules and Supramolecular Complexes . Frontiers in physiology. 2020; 11(Mar 12)); 189 . IF = 4.566 [ASEP] [ doi ]
Sinica; Viktor - Zímová; Lucie - Barvíková; Kristýna - Máčiková; Lucie - Barvík; I. - Vlachová; Viktorie . Human and Mouse TRPA1 Are Heat and Cold Sensors Differentially Tuned by Voltage . Cells. 2020; 9(1)); 57 . IF = 6.600 [ASEP] [ doi ]
Park; DH. - Park; S. - Song; JM. - Kang; M. - Lee; S. - Horák; Martin - Suh; Y. H. N-linked glycosylation of the mGlu7 receptor regulates the forward trafficking and transsynaptic interaction with Elfn1 . FASEB Journal. 2020; 34(11); 14977-14996 . IF = 5.191 [ASEP] [ doi ]
Kořínek; Miloslav - González-González; I. M. - Smejkalová; Tereza - Hajduković; Dragana - Skřenková; Kristýna - Krůšek; Jan - Horák; Martin - Vyklický ml.; Ladislav . Cholesterol modulates presynaptic and postsynaptic properties of excitatory synaptic transmission . Scientific Reports. 2020; 10(1)); 12651 . IF = 4.379 [ASEP] [ doi ]
Klempíř; O. - Krupička; R. - Krůšek; Jan - Dittert; Ivan - Petráková; V. - Petrák; V. - Taylor; Andrew . Application of Spike Sorting Algorithm to Neuronal Signals Originated from Boron Doped Diamond Micro-Electrode Arrays . Physiological Research. 2020; 69(3); 529-536 . IF = 1.881 [ASEP] [ doi ]
Hrčka Krausová; Barbora - Kysilov; Bohdan - Černý; Jiří - Vyklický; Vojtěch - Smejkalová; Tereza - Ladislav; Marek - Balík; Aleš - Kořínek; Miloslav - Chodounská; Hana - Kudová; Eva - Vyklický ml.; Ladislav . Site of Action of Brain Neurosteroid Pregnenolone Sulfate at the N-Methyl-D-Aspartate Receptor . Journal of Neuroscience. 2020; 40(31); 5922-5936 . IF = 6.167 [ASEP] [ doi ]
Barvíková; Kristýna - Barvík; I. - Sinica; Viktor - Zímová; Lucie - Vlachová; Viktorie . Phospho-Mimetic Mutation at Ser602 Inactivates Human TRPA1 Channel . International Journal of Molecular Sciences. 2020; 21(21)); 7995 . IF = 5.923 [ASEP] [ doi ]
Skřenková; Kristýna - Hemelíková; Katarína - Kolcheva; Marharyta - Kortus; S. - Kaniaková; Martina - Krausová; Barbora - Horák; Martin . Structural features in the glycine-binding sites of the GluN1 and GluN3A subunits regulate the surface delivery of NMDA receptors . Scientific Reports. 2019; 9(Aug 23)); 12303 . IF = 3.998 [ASEP] [ doi ]
Máčiková; Lucie - Vyklická; Lenka - Barvík; I. - Sobolevsky; A. I. - Vlachová; Viktorie . Cytoplasmic Inter-Subunit Interface Controls Use-Dependence of Thermal Activation of TRPV3 Channel . International Journal of Molecular Sciences. 2019; 20(16)); 3990 . IF = 4.556 [ASEP] [ doi ]
Máčiková; Lucie - Sinica; Viktor - Kádková; Anna - Villette; S. - Ciaccafava; A. - Faherty; J. - Lecomte; S. - Alves; I. D. - Vlachová; Viktorie . Putative interaction site for membrane phospholipids controls activation of TRPA1 channel at physiological membrane potentials . FEBS Journal. 2019; 286(18); 3664-3683 . IF = 4.392 [ASEP] [ doi ]
Krůšek, Jan - Dittert, Ivan - Smejkalová, Tereza - Kořínek, Miloslav - Gottfriedová, Kristýna - Freislebenová, Hana - Neuhöferová, Eva - Klimša, Ladislav - Sedláková, Silvia - Taylor, Andrew - Mortet, Vincent - Petrák, V. - Benson, Veronika - Petráková, V. Molecular Functionalization of Planar Nanocrystalline and Porous Nanostructured Diamond to Form an Interface with Newborn and Adult Neurons . Physica Status Solidi B-Basic Solid State Physics 2019, 256(3), 1800424 . IF = 1.481 [ASEP] [ doi ]
Kaniaková; Martina - Nepovímová; E. - Kletečková; L. - Skřenková; K. - Holubová; K. - Chrienová; Z. - Hepnarová; V. - Kučera; T. - Kobrlová; T. - Valeš; K. - Korábečný; J. - Soukup; O. - Horák; Martin . Combination of Memantine and 6-Chlorotacrine as Novel Multi-Target Compound against Alzheimer's Disease . Current Alzheimer Research. 2019; 16(9); 821-833 . IF = 3.047 [ASEP] [ doi ]
Chiu; A. M. - Wang; J. - Fiske; M. P. - Hubálková; Pavla - Barse; L. - Gray; J. A. - Sanz-Clemente; A. NMDAR-Activated PP1 Dephosphorylates GluN2B to Modulate NMDAR Synaptic Content . Cell Reports. 2019; 28(2); 332-341 . IF = 8.109 [ASEP] [ doi ]

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People

Head of the Laboratory

prof. MUDr. Ladislav Vyklický, DrSc.

ladislav.vyklicky@fgu.cas.cz

Deputy Head of the Laboratory
RNDr. Viktorie Vlachová, DrSc.
Senior Researcher
RNDr. Aleš Balík, Ph.D.
Ing. Ivan Dittert, Ph.D.
Mgr. Miloslav Kořínek, Ph.D.
RNDr. Jan Krůšek, Ph.D.
Tereza Smejkalová, Ph.D.
Prof. RNDr. František Vyskočil, DrSc. (emeritus)
Associated Researchers
Ing. Jiří Černý, Ph.D.
RNDr. Lenka Vyklická, Ph.D.
Mgr. Lucie Zímová, Ph.D.
Postdoctoral Fellow
Miriam Candelas Serra, Ph.D.
PhD Student
Vera Abramová, MSc.
Mark Dobrovolski, MSc.
Ing. Klevinda Fili
Mgr. Viktor Kuchtiak
Bohdan Kysilov, MSc.
Mgr. Alexandra Ptáková
Eni Tomović, MSc.
Research Assistant
Bc. Michal Mitro
Gabriela Havrilčáková
Technician
Miloslava Kuldová
Mgr. Romana Marková