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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

Lebedeva; M. - Kubištová; A. - Spišská; V. - Filipovská; E. - Pačesová; D. - Svobodová; I. - Kuchtiak; Viktor - Balík; Aleš - Bendová; Z. The disruption of circadian rhythmicity of gene expression in the hippocampus and associated structures in Gria2R/R mice; a comparison with C57BL/6J and Adar2?/? mice strains . Brain Research. 2024; 1826(1 March); 148739 . IF = 2.9 [ASEP] [ doi ]
Kysilov; Bohdan - Kuchtiak; Viktor - Hrčka Krausová; Barbora - Balík; Aleš - Kořínek; Miloslav - Fili; Klevinda - Dobrovolski; Mark - Abramová; Vera - Chodounská; Hana - Kudová; Eva - Božíková; Paulina - Černý; Jiří - Smejkalová; Tereza - Vyklický ml.; Ladislav . Disease-associated nonsense and frame-shift variants resulting in the truncation of the GluN2A or GluN2B C-terminal domain decrease NMDAR surface expression and reduce potentiating effects of neurosteroids . Cellular and Molecular Life Sciences. 2024; 81(1); 36 . IF = 8.0 [ASEP] [ doi ]
Cheema; Marie Munawar - Kotrbová Macáková; Zuzana - Hrčka Krausová; Barbora - Adla; Santosh Kumar - Slavíková; Barbora - Chodounská; Hana - Kratochvíl; Miroslav - Vondrášek; Jiří - Sedlák; David - Balaštík; Martin - Kudová; Eva . 5β-reduced neuroactive steroids as modulators of growth and viability of postnatal neurons and glia . Journal of Steroid Biochemistry and Molecular Biology. 2024; 239(May); 106464 . IF = 4.1 [ASEP] [ doi ]
Studtmann; C. - Ladislav; M. - Safari; M. - Khondaker; R. - Chen; Y. - Vaughan; G. A. - Topolski; M. A. - Tomović; E. - Balík; Aleš - Swanger; S. A. Ventral posterolateral and ventral posteromedial thalamocortical neurons have distinct physiological properties . Journal of Neurophysiology. 2023; 130(6); 1492-1507 . IF = 2.5 [ASEP] [ doi ]
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 ]

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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