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Thermally gated TRP channels in nociceptive neurones
Chvojka, Štěpán ; Vlachová, Viktorie (advisor) ; Mrózková, Petra (referee)
Transduction ion channels are gated in response to a variety of external stimuli and this process is critical for the proper functioning of sensory neurons. These specialized proteins enable the survival of any organism, which depends on having adequate information about the external environment. The thermosensitive TRP (transient receptor potential) ion channels, whose molecular structure has been identified during last decades, enable the transduction of thermal stimuli in primary nociceptive neurons. During the last decade, molecular biological techniques have provided new tools for studying the structure of these specialized transduction ion channels in relation to their function and to understand more deeply their physiological roles. The aim of this bachelor thesis is to give an overview of recent evidence regarding the functional and physiological properties of sensory-neuron specific mammalian TRP ion channels that are activated by thermal stimuli: heat and cold.
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Mechanisms of activation and modulation of vanilloid TRP channels
Boukalová, Štěpána ; Vlachová, Viktorie (advisor) ; Hock, Miroslav (referee) ; Zemková, Hana (referee)
Štěpána Boukalová Mechanisms of activation and modulation of vanilloid TRP channels TRPV1 and TRPV3 are thermosensitive ion channels from the vanilloid subfamily of TRP receptors. TRPV1, which is primarily expressed in nociceptive sensory neurons, is an important transducer of painful stimuli and is also involved in the detection of noxious heat. TRPV3 is expressed mainly in the skin where it regulates proliferation and differentiation of keratinocytes. Similarly to voltage-dependent potassium (Kv) channels, TRP receptors are comprised of four subunits, each with six transmembrane segments (S1-S6). Using mutational approach, we tried to elucidate the role of S1 in TRPV1 functioning. Our results indicate that the extracellular portion of S1 plays a crucial role in TRPV1 gating. TRPV1 channels with a conservative mutation of positively charged residue in this region (R455K substitution) were overactive. However, they were neither activated nor potentiated by low pH; on the contrary, protons stabilized the closed conformation of this mutant channel. Very similar phenotypic properties were found in other TRPV1 mutants with substitution in S4/S5-S5 region and in the pore helix. In Kv channels, extracelular portion of S1 forms a small contact surface with the pore helix, which allows efficient transmission of...
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Thermally gated TRP channels in nociceptive neurones
Chvojka, Štěpán ; Vlachová, Viktorie (advisor) ; Mrózková, Petra (referee)
Transduction ion channels are gated in response to a variety of external stimuli and this process is critical for the proper functioning of sensory neurons. These specialized proteins enable the survival of any organism, which depends on having adequate information about the external environment. The thermosensitive TRP (transient receptor potential) ion channels, whose molecular structure has been identified during last decades, enable the transduction of thermal stimuli in primary nociceptive neurons. During the last decade, molecular biological techniques have provided new tools for studying the structure of these specialized transduction ion channels in relation to their function and to understand more deeply their physiological roles. The aim of this bachelor thesis is to give an overview of recent evidence regarding the functional and physiological properties of sensory-neuron specific mammalian TRP ion channels that are activated by thermal stimuli: heat and cold.
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