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Description
| - Byly studovány molekulární mechanizmy akutní desenzitizace vaniloidního TRPV1 receptoru závislé na vápníku. Tento fyziologicky velmi významný regulační mechanizmus se uplatňuje při analgezii vyvolané lokálním působením kapsaicinu na primárních nociceptorech. Byla vyslovena hypotéza, že konformační změny, v jejichž důsledku dochází k desenzitizaci TRPV1 proteinového komplexu, zahrnují oblast vazebného místa, v jehož blízkosti se pravděpodobně nachází krátký cytoplazmatický úsek karboxylového konce navazujícího na 6. transmembránovou doménu (R701-T704). Tato doména prostřednictvím kladně nabitého aminokyselinového zbytku zajišťuje optimální (tj. vhodnou pro aktivaci iontového kanálu) interakci proteinu s lipidem plazmatické membrány fostatidylinozitol-4,5-bisfosfátem (PIP2) (cs)
- We examined the mechanisms of acute Ca2+-dependent desensitization using whole-cell patch-clamp techniques in HEK293T cells expressing the wild type or CaMKII phosphorylation site mutants of TRPV1. The nonphosphorylatable mutant S502A/T704I was capsaicin-insensitive but the S502A/T704A construct was fully functional, indicating a requirement for a specific residue at position 704. A point mutation at the nearby conserved residue R701 strongly affected the heat, capsaicin and pH-evoked currents. As this residue constitutes a stringent CaMKII consensus site but is also predicted to be involved in the interaction with membrane phosphatidylinositol 4,5-bisphosphate (PIP2), this data suggests that in addition to dephosphorylation, or as its consequence, a short C-terminal juxtamembrane segment adjacent to the TRP box comprised of R701 and T704 might be involved in the decelerated gating kinetics of the desensitized TRPV1 channel
- We examined the mechanisms of acute Ca2+-dependent desensitization using whole-cell patch-clamp techniques in HEK293T cells expressing the wild type or CaMKII phosphorylation site mutants of TRPV1. The nonphosphorylatable mutant S502A/T704I was capsaicin-insensitive but the S502A/T704A construct was fully functional, indicating a requirement for a specific residue at position 704. A point mutation at the nearby conserved residue R701 strongly affected the heat, capsaicin and pH-evoked currents. As this residue constitutes a stringent CaMKII consensus site but is also predicted to be involved in the interaction with membrane phosphatidylinositol 4,5-bisphosphate (PIP2), this data suggests that in addition to dephosphorylation, or as its consequence, a short C-terminal juxtamembrane segment adjacent to the TRP box comprised of R701 and T704 might be involved in the decelerated gating kinetics of the desensitized TRPV1 channel (en)
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Title
| - Functional changes in the vanilloid receptor subtype 1 channel during and after acute desensitization
- Funkční změny vaniloidního receptoru podtypu 1 (TRPV1) v průběhu akutní desenzitizace (cs)
- Functional changes in the vanilloid receptor subtype 1 channel during and after acute desensitization (en)
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skos:prefLabel
| - Functional changes in the vanilloid receptor subtype 1 channel during and after acute desensitization
- Funkční změny vaniloidního receptoru podtypu 1 (TRPV1) v průběhu akutní desenzitizace (cs)
- Functional changes in the vanilloid receptor subtype 1 channel during and after acute desensitization (en)
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skos:notation
| - RIV/67985823:_____/07:00094541!RIV08-AV0-67985823
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http://linked.open.../vavai/riv/strany
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http://linked.open...avai/riv/aktivita
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http://linked.open...avai/riv/aktivity
| - P(1M0517), P(GA303/07/0915), P(GA305/06/0319), P(LC06010), P(LC554), R, Z(AV0Z50110509), Z(AV0Z60870520)
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http://linked.open...iv/cisloPeriodika
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http://linked.open...vai/riv/dodaniDat
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http://linked.open...aciTvurceVysledku
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http://linked.open.../riv/druhVysledku
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http://linked.open...iv/duvernostUdaju
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http://linked.open...titaPredkladatele
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http://linked.open...dnocenehoVysledku
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http://linked.open...ai/riv/idVysledku
| - RIV/67985823:_____/07:00094541
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http://linked.open...riv/jazykVysledku
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http://linked.open.../riv/klicovaSlova
| - capsaicin; vanilloid receptor; TRP channels (en)
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http://linked.open.../riv/klicoveSlovo
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http://linked.open...odStatuVydavatele
| - GB - Spojené království Velké Británie a Severního Irska
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http://linked.open...ontrolniKodProRIV
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http://linked.open...i/riv/nazevZdroje
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http://linked.open...in/vavai/riv/obor
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http://linked.open...ichTvurcuVysledku
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http://linked.open...cetTvurcuVysledku
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http://linked.open...vavai/riv/projekt
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http://linked.open...UplatneniVysledku
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http://linked.open...v/svazekPeriodika
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http://linked.open...iv/tvurceVysledku
| - Benedikt, Jan
- Samad, Abdul
- Teisinger, Jan
- Vlachová, Viktorie
- Vyklický st., Ladislav
- Sušánková, Klára
- Toušová, Karolina
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http://linked.open...n/vavai/riv/zamer
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issn
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number of pages
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