کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4341205 | 1295827 | 2007 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Functional changes in the vanilloid receptor subtype 1 channel during and after acute desensitization
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کلمات کلیدی
transient receptor potential vanilloid receptor-1TRPV1TrpGFPHEKCaMKIIpKaPIP2PKCCa2+/Calmodulin-dependent kinase II - Ca2 + / Calmodulin وابسته به کیناز III–V - I - Vcurrent–voltage - جریان ولتاژStructure-function relationship - ساختار-عملکرد رابطهphosphatidylinositol 4,5-bisphosphate - فسفاتیدیلینوزیتول 4،5-بیسفسفاتtransient receptor potential - پتانسیل گیرنده گذراgreen fluorescent protein - پروتئین فلورسنت سبزprotein kinase A - پروتئین کیناز AProtein kinase C - پروتئین کیناز سیTRP channels - کانال های TRPDesensitization - کاهش حساسیتhuman embryonic kidney - کلیه جنین انسانCapsaicin - کپسایسین یا کاپسیسینVanilloid receptor - گیرنده وانیلیوئید
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
Agonist-induced desensitization of the transient receptor potential vanilloid receptor-1 (TRPV1) is one of the key strategies that offer a way to alleviate neuropathic and inflammatory pain. This process is initiated by TRPV1 receptor activation and the subsequent entry of extracellular Ca2+ through the channel into sensory neurones. One of the prominent mechanisms responsible for TRPV1 desensitization is dephosphorylation of the TRPV1 protein by the Ca2+/calmodulin-dependent enzyme, phosphatase 2B (calcineurin). Of several consensus phosphorylation sites identified so far, the most notable are two sites for Ca2+/calmodulin dependent kinase II (CaMKII) at which the dynamic equilibrium between the phosphorylated and dephosphorylated states presumably regulates agonist binding. We examined the mechanisms of acute Ca2+-dependent desensitization using whole-cell patch-clamp techniques in human embryonic kidney (HEK) 293T cells expressing the wild type or CaMKII phosphorylation site mutants of rat 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), these data suggest that in addition to dephosphorylation, or as its consequence, a short C-terminal juxtamembrane segment adjacent to the transient receptor potential box composed of R701 and T704 might be involved in the decelerated gating kinetics of the desensitized TRPV1 channel.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 149, Issue 1, 12 October 2007, Pages 144-154
Journal: Neuroscience - Volume 149, Issue 1, 12 October 2007, Pages 144-154
نویسندگان
K. Novakova-Tousova, L. Vyklicky, K. Susankova, J. Benedikt, A. Samad, J. Teisinger, V. Vlachova,