National Repository of Grey Literature 20 records found  1 - 10next  jump to record: Search took 0.00 seconds. 
A study of the temperature sensitivity of the human TRPA1 channel
Barvíková, Kristýna ; Šulc, Miroslav (advisor) ; Černá, Věra (referee)
Transient receptor potential (TRP) ion channels play important physiological roles in the detection of environmental stimuli that occur primarily at the peripheral terminals of specialized sensory neurons. The recently resolved cryo-electron microscopy structures and molecular biological techniques have provided new tools that enable to study these channels in relation to their function, and thus to understand more deeply their pharmacology and physiology. The aim of this bachelor thesis is to give an overview of the current status of research on the ankyrin TRP channel subtype 1 (TRPA1), a channel activated by diverse irritant chemical stimuli but also by temperature changes. The experimental part is focused on the elucidation of the role of the sensor domain in thermal sensitivity of the TRPA1 channel. Using whole-cell patch-clamp electrophysiological technique, the presented results demonstrate that the sensor is an important determinant of voltage-dependent gating. Mutation of the conserved tyrosine in the center of the sensor resulted in channels with clearly different activation kinetics and increased chemical responses upon increasing the temperature from 25 řC to 35 řC. Key words: TRP ion channel, ankyrin receptor, nociception, structure-function, carvacrol
The role of nociceptive synaptic transmission modulation
Tyshkevich, Alexandra ; Paleček, Jiří (advisor) ; Hejnová, Lucie (referee)
Chronic pain phenomenon is an important problem in modern medicine. Occurring of this phenomenon is tightly connected with nociceptive transmission and modulation of nociceptive signal on the spinal cord level. Under the pathological conditions such as injury or inflammation this modulation is affected by different types of endogenous molecules with pain enhancing attributes. Important group of these molecules are chemokines, immune system substances, also responsible for immune cells recruitments. However, in pathological states chemokines show ability to modulate nociceptive signal and induce chronic pain. CCL2, in particular, has a significant role in modulation of these processes in the spinal cord. Investigation of the mechanisms by which CCL2 influences the spinal cord and dorsal root ganglion may be an important part for preventing the development of chronic pain. Key words: nociception, pain, spinal cord, chemokines, CCL2
The role of spinal TRPV1 receptors in nociceptive signalling and the modulatory effect of chemokine CCL2 and µ-opioid receptor agonists
Šulcová, Dominika ; Paleček, Jiří (advisor) ; Krůšek, Jan (referee)
The first nociceptive synapse in the spinal cord dorsal horn represents an important site, where nociceptive synaptic transmission can be modulated under pathological conditions. One of the modulatory mechanism involves activation of the transient receptor potential vanilloid 1 (TRPV1) that is expressed on central terminals of primary nociceptive neurons, where it regulates release of neurotransmitters and neuromodulators. Previous studies suggested that changes in TRPV1 activity may be related to effects of chemokine CCL2 (C-C motif ligand 2) and may be also involved in synaptic transmission modulation after µ-opioid receptors (MOP-R) activation. Because CCL2 receptors CCR2 often co-localize with TRPV1 and MOP-R, the goal of this work was to studypossible interactions of these receptors on the pre-synaptic endings of primaryafferents in the spinal cord dorsal horn and their role in nociceptive signalling under pathological conditions. The presented thesis focused on the effect of CCL2 during peripheral neuropathy and its interference with µ-opioid receptor activation. To studysynaptic transmission at the spinal cord level, patch-clamp recordings of excitatory post-synaptic currents (EPSC) in superficial spinal cord dorsal horn neurons in acute lumbar spinal cord slices from rats was used....
Functional and structural study of thermally activated TRP ion channels: The role evolutionarily conserved motifs in the TRPA1 modulation
Kádková, Anna ; Vlachová, Viktorie (advisor) ; Hudeček, Jiří (referee) ; Obšilová, Veronika (referee)
Ankyrin receptor TRPA1 is an ion channel widely expressed on primary afferent sensory neurons, where it acts as a polymodal sensor of nociceptive stimuli. Apart from pungent chemicals (e. g. isothiocyanates, cinnamaldehyde and its derivatives, acrolein, menthol), it could be activated by cold temperatures, depolarizing voltages or intracellular calcium ions. TRPA1 channel is a homotetramer in which each subunit consists of cytoplasmic N and C termini and a transmembrane region. The transmembrane part is organized into six alpha- helices connected by intra- and extracellular loops. The N terminus comprises a tandem set of 16 to 17 ankyrin repeats (AR), while the C terminus has a substantially shorter, dominantly helical structure. In 2015, a partial cryo-EM structure of TRPA1 was resolved; however, the functional roles of the individual regions of the receptor have not yet been fully understood. This doctoral thesis is concerned to elucidate the role of highly conserved sequence and structural motifs within the cytoplasmic termini and the S4-S5 region of TRPA1 in voltage- and chemical sensitivity of the receptor. The probable binding site for calcium ions that are the most important physiological modulators of TRPA1 was described by using homology modeling, molecular-dynamics simulations,...
The role of TLR-4 receptors for modulation of nociceptive signalling.
Slepička, Jakub ; Paleček, Jiří (advisor) ; Zímová, Lucie (referee)
The ability to feel pain is subjective, but a crucial factor allowing us to maintain life with minimal body impairment. However, if the pain crosses the physiological signalling function it becomes a life restrictive symptom that is often difficult to treat. Development of pain and its change into pathological chronic symptom and the role of different molecular and cellular mechanisms in this process are best to be studied during its development, nociception. In this work the basic characteristics of nociceptive signalling, with focus on neuropathy, a state originating from nervous system damage is given. The exact mechanisms of neuropathic pain development are not known, which is one of the reasons why these painful states are difficult to treat. Neuroinflammation was lately shown to play an important part in the neuropathy development. In this context a review of Toll-like receptors is given. These receptors have a fundamental role in the innate immunity and their role in the nervous system was documented recently. In this review a focus is given on TLR-4 subtype that was shown to be involved in a modulation of nociceptive signalling. The basic features of this receptor and information about its involvement in neuropathic pain development are given. Studying the role of TLR-4 in different models...
Molecular physiology of low-voltage-activated T-type channels in neuropathic pain
Pelant, Tomáš ; Weiss, Norbert (advisor) ; Fišer, Radovan (referee)
Low-voltage activated T-type channels contribute significantly to signal transmission in ascending pain pathway. Their electrophysiological and biochemical properties allow them to modulate neuronal excitability and neurotransmitter release. Alterations of electric currents associated with a number of neuronal disorders, including neuropathic pain and epilepsy, have been linked to this subtype of calcium channel, suggesting its prominent role in modulation of neuronal response to various noxious stimuli. Multiple diseases, such as diabetes, cancer or chronic nerve injury, are accompanied by painful neuropathic conditions. Specific inhibitors of T-type channels have been demonstrated to alleviate symptoms of neuropathic pain in mouse models, showing their potential for development of novel type of drugs possibly more effective than traditional analgesics, which exhibit minor effect in neuropathic pain treatment.
Structural basis for interspecies differences in the TRPA1 receptor activation
Synytsya, Viktor ; Šulc, Miroslav (advisor) ; Hudeček, Jiří (referee)
Ankyrin transient receptor potential channel TRPA1 is an excitatory ion channel that transduces nociceptive information on primary aferent sensory nerves of mammals and other organisms. Structure function studies on TRPA1 are valuable for understanding the mechanisms of channel activation and for specific drug discovery efforts, however, significant interspecies differences hamper direct transfer of findings in animals to human. On the other hand, the interspecies differences may prompt identification of many important functional domains. The aim of this bachelor thesis is to give an overview of recent evidence regarding the functional and structural properties of human TRPA1 ion channels from the point of view of the comparison of the most important interspecies differences among TRPA1 orthologs. The experimental part is focused on the comparison of activation properties of human TRPA1 channel with a chimera in which the fifth transmembrane region was replaced by that from Drosophila melanogaster. The presented results obtained by electrophysiological technique patch-clamp demonstrate that outward membrane currents induced by depolarizing voltage are significantly reduced in chimera, which indicates an important role of the fifth transmembrane domain in TRPA1 channel gating (In Czech). Key words:...
Functional role of cytoplasmic domains in the gating of TRPA1 channel
Vašková, Jana ; Vlachová, Viktorie (advisor) ; Zemková, Hana (referee)
The transient receptor potential ankyrin 1 (TRPA1) ion channel is expressed in a subset of primary afferent neurones where it is activated by a variety of pungent and chemically reactive compounds such as allyl isothiocyanate or cinnamaldehyde. This voltage- dependent channel is activated through covalent modification of cytoplasmic cysteines and, from the cytoplasmic side, is also critically regulated by calcium ions. Both, amino (N-) and carboxyl (C-) termini have been shown to be involved in these processes. Using electrophysiological and molecular-biology techniques, we explored the role of specific cytoplasmic domains in the activation of TRPA1. By measuring chemically-, voltage-, and calcium-activated membrane TRPA1-mediated currents, we identified highly conserved serine and threonine residues along the N-terminal ankyrin repeat domain, mutation of which strongly affected responses of the channel. In addition, using C-terminally truncated construct previously reported to be involved in calcium regulation, we present a new finding that the distal C-terminal tail contributes to voltage-dependent activation of TRPA1.
Local changes of selected somatesthetic parameters in response to stretching m. quadriceps fenoris
Vaňková, Karolína ; Čech, Zdeněk (advisor) ; Lepšíková, Magdaléna (referee)
Fascial tissues form a continuous whole-body three-dimensional network penetrating all parts of the human body. They include all fibrous connective tissue that significantly contributes both to themaintaining of the integrity of the organism and the functioning of body systems and the somesthetic perception.That is because of the facia is richly populated by proprioceptiveand mechanosensitive nociceptive nerve endings. Although the stretching is a routine method used in sports and rehabilitation, its exact mechanism of influence and effects on the body are not fully understood so far. Stretching exercises affect the mechanical state of the myofascial tissues and also the quality of the nociception and proprioception by alteration of their preload. There is evidence about some differences of the mechanical properties of the tissuesboth between thesexes and hypermobile individuals. The theses assesses the effect of static stretching m. QF on the somesthetic perception by measuring pressure pain threshold (PPT) using pressure algometry and the quality of propcioception bygoniometric measurement considering the interindividual variance in quality of the connective tissues. Our research includes testing of 29 healthy subjects (14 women and 15 men) and it has proved significant impact of the intervention on the...
The role of TRPV1 receptors in chemokine CCL2 induced modulation of nociceptive synaptic transmission at spinal cord level
Adámek, Pavel ; Paleček, Jiří (advisor) ; Krůšek, Jan (referee)
Modulation of nociceptive synaptic transmission in the spinal cord dorsal horn is a significant mechanism in the development and maintenance of different pathological pain states. Accumulating evidence indicates that the TRPV1 (transient receptor potential vanilloid 1) receptor and chemokine CCL2 (C-C motif ligand 2) may play a critical role in this process. The aim of this diploma thesis was to investigate the CCL2 induced modulation of nociceptive synaptic transmission in the dorsal horn of spinal cord and the role of the TRPV1 receptors. To investigate this aim patch-clamp recordings of spontaneous and miniature excitatory postsynaptic currents (sEPSC, mEPSC) from superficial dorsal horn neurons in acute rat lumbar spinal cord slices were used. After acute application of CCL2 on the slice preparation from naïve animals, a frequency increase of both sEPSC and mEPSC was present. This CCL2 induced increase in both sEPSC and mEPSC frequency was prevented by the TRPV1 receptor antagonist SB366791 application. No changes were observed in the amplitudes of sEPSC or mEPSC after application of the CCL2, SB366791, or co-application of CCL2 and SB366791. This suggests that the observed changes were mediated predominantly by presynaptic mechanisms. The preliminary results indicate that after chronic constriction...

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