National Repository of Grey Literature 4 records found  Search took 0.00 seconds. 
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...
Behavioral expression of pain in rats
Zámečník, Jakub ; Vaculín, Šimon (advisor) ; Boukalová, Štěpána (referee)
The aim of this work is to summarize the current knowledge regarding the behavioral expressions of pain in rat. The work is focused on rats, because they are one of the most used laboratory animals, and may experience pain in some experiments. Behavioral expressions of pain were selected, because they are quite easily recognizable and measurable. The reader will be first acquainted with the necessary basics associated with the phenomenon of pain, with its conception in animals, with classification, physiology and for example with the ways in which are in rats experimentally induced pain. Then in the second part, there are shown individual behavioral expressions with examples in which cases were these manifestations observed. So everyone who is interested can learn something about pain in connection with the avoidance reaction, pose, appearance, specific movements of rat, vocalization, changes in eating and drinking, changes in activity, anxiety, cognitive functions and many other expressions. The work can be valuable contribution for all workers with animals and with its character can contribute to animal welfare. Powered by TCPDF (
The role of conserved residues in the S4/S4-S5 region of vanilloid TRP channels
Boukalová, Štěpána ; Doležal, Vladimír (referee) ; Vlachová, Viktorie (advisor)
The vanilloid transient receptor potential channel TRPV1 is a tetrameric six-transmembrane segment (S1-S6) channel that can be synergistically activated by various proalgesic agents such as capsaicin, protons, heat or highly depolarizing voltages. In TRPV1 channel, the charged residues in the S4 region and intracellular S4-S5 linker have been proposed to constitute a part of a voltage sensor that acts in concert with other stimuli to regulate channel activation. Molecular basis of this gating event are poorly understood. We mutated charged residues all along the S4 and the S4-S5 linker of TRPV1 and related vanilloid receptors to identify potential voltage-sensing residues. The functionality of most of the TRPV1 mutants was altered with respect to voltage, capsaicin, heat and/or their interactions. We identified two amino acid residues (R557 and D576) that could potentially constitute part of TRPV1 voltage sensor. The non-functional charge-reversing mutations R557E and R579E were partially rescued by charge-swapping mutations R557E/E570R and D576R/R579E, indicating that electrostatic interactions contribute to allosteric coupling between the voltage-, temperature- and capsaicin-dependent activation mechanisms. The mutant K571E was normal in all aspects of TRPV1 activation except for 2aminoethoxydiphenyl...

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