کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5508791 | 1400400 | 2016 | 50 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Privileged crosstalk between TRPV1 channels and mitochondrial calcium shuttling machinery controls nociception
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کلمات کلیدی
TRPV1DRGMCUNCLXCGP37157FCCPAAVRyRmitochondrial Ca2 + uniporterIP3R2-APB2-aminoethoxydiphenyl borate[Ca2 +]Cdorsal root ganglion - گانگلیون ریشه پشتیPain - دردnociception - غربالگریAdeno-associated virus - ویروس Adeno مرتبط استCarbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone - کربونیل سیانید 4- (trifluoromethoxy) phenylhydrazonecarbonyl cyanide m-chlorophenyl hydrazone - کربونیل سیانید m-کلروفنیل هیدرازونCapsaicin - کپسایسین یا کاپسیسینinositol 1,4,5-trisphosphate receptors - گیرنده های inositol 1،4،5-trisphosphateRyanodine receptors - گیرنده های رایانودین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The nociceptive noxious heat-activated receptor - TRPV1, conducts calcium and sodium, thus producing a depolarizing receptor potential, leading to activation of nociceptive neurons. TRPV1-mediated calcium and sodium influx is negatively modulated by calcium, via calcium-dependent desensitization of TRPV1 channels. A mitochondrial Ca2Â + uniporter - MCU, controls mitochondrial Ca2Â + entry while a sodium/calcium transporter - NCLX shapes calcium and sodium transients by mediating sodium entry into and removing calcium from the mitochondria. The functional interplay between TRPV1, MCU and NCLX, in controlling the cytosolic and mitochondrial calcium and sodium transients and subsequently the nociceptive excitability, is poorly understood. Here, we used cytosolic and mitochondrial fluorescent calcium and sodium imaging together with electrophysiological recordings of TRPV1-induced currents in HEK293T cells and nociceptor-like dissociated rat dorsal root ganglion neurons, while modulating NCLX or MCU expression using specific small interfering RNA (siNCLX). We show that the propagation of the TRPV1-induced cytosolic calcium and sodium fluxes into mitochondria is dependent on coordinated activity of NCLX and MCU. Thus, knocking-down of NCLX triggers down regulation of MCU dependent mitochondrial Ca2Â + uptake. This in turn decreases rate and amplitude of TRPV1-mediated cytosolic calcium, which inhibits capsaicin-induced inward current and neuronal firing. TRPV1-mediated currents were fully rescued by intracellular inclusion of the fast calcium chelator BAPTA. Finally, NCLX controls capsaicin-induced cell death, by supporting massive mitochondrial Ca2Â + shuttling. Altogether, our results suggest that NCLX, by regulating cytosolic and mitochondrial ionic transients, modulates calcium-dependent desensitization of TRPV1 channels, thereby, controlling nociceptive signaling.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1863, Issue 12, December 2016, Pages 2868-2880
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1863, Issue 12, December 2016, Pages 2868-2880
نویسندگان
Iulia I. Nita, Yaki Caspi, Sagi Gudes, Dimitri Fishman, Shaya Lev, Michal Hersfinkel, Israel Sekler, Alexander M. Binshtok,