{"id":1536,"date":"2017-10-26T17:20:09","date_gmt":"2017-10-26T08:20:09","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=1536"},"modified":"2017-10-26T17:20:09","modified_gmt":"2017-10-26T08:20:09","slug":"journal-club-2017-10-27","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=1536","title":{"rendered":"Journal Club 2017.10.27"},"content":{"rendered":"

Contribution<\/span>\u00a0of\u00a0TRPC3<\/span>\u00a0to\u00a0store-operated<\/span>\u00a0calcium<\/span>\u00a0entry and inflammatory transductions in primary nociceptors.<\/h1>\n
Alkhani H<\/a>,\u00a0Ase AR<\/a>,\u00a0Grant R<\/a>,\u00a0O’Donnell D<\/a>,\u00a0Groschner K<\/a>,\u00a0S\u00e9gu\u00e9la P<\/a>1<\/span><\/sup><\/div>\n
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<\/div>\n<\/div>\n
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Abstract<\/h3>\n
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BACKGROUND:<\/h4>\n

Prolonged intracellular\u00a0calcium<\/span>\u00a0elevation contributes to sensitization of nociceptors and chronic pain in inflammatory conditions. The underlying molecular mechanisms remain unknown but\u00a0store-operated<\/span>\u00a0calcium<\/span>\u00a0entry (SOCE) components participate in\u00a0calcium<\/span>\u00a0homeostasis, potentially playing a significant role in chronic pain pathologies. Most G protein-coupled receptors activated by inflammatory mediators trigger\u00a0calcium<\/span>-dependent signaling pathways and stimulate SOCE in primary afferents. The aim of the present study was to investigate the role of\u00a0TRPC3<\/span>, a\u00a0calcium<\/span>-permeable non-selective cation channel coupled to phospholipase C and highly expressed in DRG, as a link between activation of pro-inflammatory metabotropic receptors and SOCE in nociceptive pathways.<\/p>\n

RESULTS:<\/h4>\n

Using in situ hybridization, we determined that\u00a0TRPC3<\/span>\u00a0and TRPC1 constitute the major TRPC subunits expressed in adult rat DRG.\u00a0TRPC3<\/span>\u00a0was found localized exclusively in small and medium diameter sensory neurons. Heterologous overexpression of\u00a0TRPC3<\/span>channel subunits in cultured primary DRG neurons evoked a significant increase of Gd3+-sensitive SOCE following thapsigargin-induced\u00a0calcium<\/span>\u00a0store depletion. Conversely, using the same\u00a0calcium<\/span>\u00a0add-back protocol, knockdown of endogenous\u00a0TRPC3<\/span>\u00a0with shRNA-mediated interference or pharmacological inhibition with the selective\u00a0TRPC3<\/span>\u00a0antagonist Pyr10 induced a substantial decrease of SOCE, indicating a significant role of\u00a0TRPC3<\/span>\u00a0in SOCE in DRG nociceptors. Activation of P2Y2 purinoceptors or PAR2 protease receptors triggered a strong increase in intracellular\u00a0calcium<\/span>\u00a0in conditions of\u00a0TRPC3<\/span>\u00a0overexpression. Additionally, knockdown of native\u00a0TRPC3<\/span>\u00a0or its selective pharmacological blockade suppressed UTP- or PAR2 agonist-evoked\u00a0calcium<\/span>\u00a0responses as well as sensitization of DRG neurons. These data show a robust link between activation of pro-inflammatory receptors and\u00a0calcium<\/span>\u00a0homeostasis through\u00a0TRPC3<\/span>-containing channels operating both in receptor- and\u00a0store-operated<\/span>\u00a0mode.<\/p>\n

CONCLUSIONS:<\/h4>\n

Our findings highlight a major\u00a0contribution<\/span>\u00a0of\u00a0TRPC3<\/span>\u00a0to neuronal\u00a0calcium<\/span>\u00a0homeostasis in somatosensory pathways based on the unique ability of these cation channels to engage in both SOCE and receptor-operated\u00a0calcium<\/span>\u00a0influx. This is the first evidence for\u00a0TRPC3<\/span>\u00a0as a SOCE component in DRG neurons. The flexible role of\u00a0TRPC3<\/span>\u00a0in\u00a0calcium<\/span>\u00a0signaling as well as its functional coupling to pro-inflammatory metabotropic receptors involved in peripheral sensitization makes it a potential target for therapeutic strategies in chronic pain conditions.<\/p>\n

Contribution of TRPC3 to SOCE and inflammatory transductions in primary nociceptors<\/a><\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Contribution\u00a0of\u00a0TRPC3\u00a0to\u00a0store-operated\u00a0calcium\u00a0entry and inflammatory transductions in primary nociceptors. Alkhani H,\u00a0Ase AR,\u00a0Grant R,\u00a0O’Donnell D,\u00a0Groschner K,\u00a0S\u00e9gu\u00e9la P1 Abstract BACKGROUND: Prolonged intracellular\u00a0calcium\u00a0elevation contributes to sensitization of nociceptors and chronic pain in inflammatory conditions. The underlying molecular mechanisms remain unknown but\u00a0store-operated\u00a0calcium\u00a0entry (SOCE) components participate in\u00a0calcium\u00a0homeostasis, potentially playing a significant role in chronic pain pathologies. Most G protein-coupled receptors activated by […]<\/p>\n","protected":false},"author":5,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}}},"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1536"}],"collection":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1536"}],"version-history":[{"count":1,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1536\/revisions"}],"predecessor-version":[{"id":1537,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1536\/revisions\/1537"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1536"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1536"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1536"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}