{"id":449,"date":"2018-01-10T12:41:04","date_gmt":"2018-01-10T12:41:04","guid":{"rendered":"http:\/\/confolab.sav.sk\/ovsb\/?page_id=449"},"modified":"2023-10-06T14:09:26","modified_gmt":"2023-10-06T14:09:26","slug":"hhmi-55000343","status":"publish","type":"page","link":"https:\/\/confolab.sav.sk\/ovsb\/projekty\/ukoncene-projekty\/hhmi-55000343\/","title":{"rendered":"HHMI-55000343"},"content":{"rendered":"<p><script type=\"text\/javascript\">\n<!--\nfunction launch(newURL, newName, newFeatures, orgName) {\n  var remote = open(newURL, newName, newFeatures);\n  if (remote.opener == null)\n    remote.opener = window;\n  remote.opener.name = orgName;\n  return remote;\n}\n\nfunction launchRemote(name) {\n  var address =  name;\n  myRemote = launch(address ,\n                    \"Okno\",\n                    \"height=500, width=850, left=50, top=50, alwaysLowered=0, alwaysRaised=0, channelmode=0, dependent=0, directories=0, fullscreen=0, hotkeys=1, location=0, menubar=0, resizable=0, scrollbars=0, status=0, titlebar=1, toolbar=0, z-lock=0\",\n                    \"myWindow\");\n}\n\/\/ -->>\n<\/script><\/p>\n<h2>Molekul\u00e1rny mechanizmus v\u00e1pnikovej signaliz\u00e1cie a v\u00e4zba excit\u00e1cie s kontrakciou na srdci &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<button onclick=\"goBack()\">Nasp\u00e4t<\/button> <\/h2>\n<p><script>\t \t \nfunction goBack() { window.history.go(-1); }\t \t \n<\/script><\/p>\n<table border=\"0\" width=\"100%\" cellspacing=\"1\" cellpadding=\"2\">\n<tbody>\n<tr>\n<td>\n<h3>Ved\u00faci projektu: <a href=\"https:\/\/confolab.sav.sk\/ovsb\/pracovnici\/vyskumnici\/ing-alexandra-zahradnikova-drsc\/\">Alexandra Zahradn\u00edkov\u00e1<\/a><\/h3>\n<h3>Trvanie: janu\u00e1r 2001 &#8211; december 2005<\/h3>\n<h3>Koordinuj\u00faca organiz\u00e1cia: \u00dastav molekul\u00e1rnej fyziol\u00f3gie a genetiky SAV, Bratislava<\/h3>\n<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Anot\u00e1cia:<\/span><\/h3>\n<p><span class=\"H3\">Anot\u00e1cia:<\/span>Vyvolanie bunkovej kontrakcie v cicav\u010dom srdci je sprostredkovan\u00e9 elektrickou excit\u00e1ciou a n\u00e1slednou v\u00e1pnikovou signaliz\u00e1ciou medzi nap\u00e4\u0165ovo z\u00e1visl\u00fdmi v\u00e1pnikov\u00fdmi kan\u00e1lmi (DHPR) povrchovej membr\u00e1ny a ryanod\u00ednov\u00fdmi receptormi (RyR) sarkoplazmatick\u00e9ho retikula. Cie\u013eom tohto projektu je porozumie\u0165, ako je tento stochastick\u00fd proces riaden\u00fd. Pou\u017eijeme tri komplement\u00e1rne pr\u00edstupy: (1) anal\u00fdzu Ca2+ pr\u00fadov a vn\u00fatrobunkov\u00fdch v\u00e1pnikov\u00fdch sign\u00e1lov v izolovan\u00fdch cicav\u010d\u00edch srdcov\u00fdch myocytoch; (2) charakteriz\u00e1ciu jednotkov\u00fdch DHPR kan\u00e1lov v membr\u00e1ne myocytov met\u00f3dou &#8222;patch clamp&#8220; a jednotkov\u00fdch RyR kan\u00e1lov v plan\u00e1rnych lipidick\u00fdch dvojvrstv\u00e1ch; a (3) matematick\u00e9 modelovanie a po\u010d\u00edta\u010dov\u00fa simul\u00e1ciu od \u00farovne jednotkov\u00fdch kan\u00e1lov po \u00farove\u0148 celej bunky. Ur\u010d\u00edme element\u00e1rny mechanizmus Ca2+ signaliz\u00e1cie v klastroch DHPR a RyR kan\u00e1lov a jej vz\u0165ah k spriahnutiu excit\u00e1cie s kontrakciou na \u00farovni celej bunky. Tento v\u00fdskum poskytne nov\u00e9 z\u00e1kladn\u00e9 poznatky o grad\u00e1cii a efekt\u00edvnosti spriahnutia excit\u00e1cie s kontrakciou v srdci s mo\u017en\u00fdm n\u00e1sledn\u00fdm vyu\u017eit\u00edm v kardiol\u00f3gi\u00ed.<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">K\u013e\u00fa\u010dov\u00e9 slov\u00e1:<\/span><\/h3>\n<p>ryanod\u00ednov\u00fd receptor, srdcov\u00e9 myocyty, v\u00e4zba excit\u00e1cie s kontrakciou<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Ciele:<\/span><\/h3>\n<p>K spriahnutiu excit\u00e1cie s kontrakciou v cicav\u010dom srdcovom svale doch\u00e1dza v \u0161pecializovan\u00fdch tubulo-retikul\u00e1rnych spojeniach. Je sprostredkovan\u00e9 v\u00e1pnikovou signaliz\u00e1ciou medzi v\u00e1pnikov\u00fdmi kan\u00e1lmi plazmatickej membr\u00e1ny (DHPR) a pri\u013eahl\u00fdmi ryanod\u00ednov\u00fdmi receptormi (RyR) v cistern\u00e1ch sarkoplazmatick\u00e9ho retikula. Napriek pozit\u00edvnej sp\u00e4tnej v\u00e4zbe inherentnej mechanizmu v\u00e1pnikom indukovan\u00e9ho uvo\u013enenia v\u00e1pnika, E-C v\u00e4zba je plynulo gradovan\u00e1 zmenami amplit\u00fady a trvania stimula\u010dn\u00e9ho sign\u00e1lu. Kone\u010dn\u00fdm cie\u013eom tohto projektu je porozumie\u0165, ako sa dosahuje efekt\u00edvne spriahnutie excit\u00e1cie s kontrakciou. Ur\u010d\u00edme k\u013e\u00fa\u010dov\u00e9 mechanizmy v\u00e1pnikovej signaliz\u00e1cie medzi DHPR a RyR na \u0161tyroch \u00farovniach: (1) Riadenie aktiv\u00e1cie RyR jednotkov\u00fdm DHPR Ca-pr\u00fadom. (2) Inaktiv\u00e1cia DHPR v\u00e1pnikov\u00fdmi i\u00f3nmi uvo\u013enen\u00fdmi z RyR. (3) Spriahnutie a synchroniz\u00e1cia aktiv\u00e1cie a inaktiv\u00e1cie jednotliv\u00fdch RyR v jednej di\u00e1de. (4) Synchroniz\u00e1cia uvo\u013e\u0148ovania v\u00e1pnika v jednotliv\u00fdch di\u00e1dach v myocyte stimula\u010dn\u00fdm sign\u00e1lom. Tento v\u00fdskum poskytne nov\u00e9 poznatky o riaden\u00ed srdcovej E-C v\u00e4zby v\u00e1pnikom a m\u00f4\u017ee pon\u00faknu\u0165 origin\u00e1lne terapeutick\u00e9 strat\u00e9gie, ako obnovi\u0165 norm\u00e1lnu E-C v\u00e4zbu pri srdcov\u00fdch ochoreniach.<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Publik\u00e1cie:<\/span><\/h3>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<table class=\"list\" border=\"0\" width=\"100%\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18048694\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-1119\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/JPharmExpTher.jpg\" alt=\"JPharmExpTher\" width=\"75\" height=\"98\" \/><\/a><\/td>\n<td class=\"two\"><strong>Zahradnik I<\/strong>, <strong>Minarovic I<\/strong>, <strong>Zahradnikova A<\/strong> (2008). <a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18048694\")'>Inhibition of the cardiac L-type calcium channel current by antidepressant drugs.<\/a><i> J Pharmacol Exp Ther.<\/i> 324:977-984.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17034755?dopt=Citation\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-1113\" src=\"https:\/\/ars.els-cdn.com\/content\/image\/1-s2.0-S0005273606X07319-cov150h.gif\" alt=\"JPhysiol3\" width=\"75\" height=\"95\" \/><\/a><\/td>\n<td class=\"two\"><strong>Valent I<\/strong>, <strong>Zahradnikova A<\/strong>, <strong>Pavelkova J<\/strong>, <strong>Zahradnik I<\/strong> (2007): <a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17034755?dopt=Citation\")'>Spatial and temporal Ca2+, Mg2+, and ATP(2-) dynamics in cardiac dyads during calcium release.<\/a><i> Biochim Biophys Acta-Biomembr.<\/i> 1768: 155-166.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17475903?dopt=Citation\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-1113\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/JPharmExpTher-77x100.jpg\" alt=\"JPhysiol3\" width=\"75\" height=\"95\" \/><\/a><\/td>\n<td class=\"two\"><strong>Zahradnikova A<\/strong>, <strong>Minarovic I<\/strong>, <strong>Zahradnik I<\/strong> (2007): <a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17475903?dopt=Citation\")'>Competitive and cooperative effects of bay k8644 on the L-type calcium channel current inhibition by calcium channel antagonists.<\/a><i> J Pharmacol Exp Ther.<\/i> 322: 638-645.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17124272\")'><img decoding=\"async\" class=\"alignnone wp-image-1113\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/JPhysiol3.jpg\" alt=\"JPhysiol3\" width=\"75\" \/><\/a><\/td>\n<td class=\"two\"><strong>Zahradnikova A Jr<\/strong>, <strong>Polakova E<\/strong>, <strong>Zahradnik I<\/strong>, <strong>Zahradnikova A<\/strong> (2007). <a href='javascript:launchRemote(\"httsp:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17124272\")'>Kinetics of calcium spikes in rat cardiac myocytes.<\/a><i> J Physiol<\/i> 578: 677-691.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16260840?dopt=Citation\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-1114\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/JGP-125x150.jpg\" alt=\"JGP\" width=\"75\" height=\"98\" \/><\/a><\/td>\n<td class=\"two\"><strong>Zahradnik I<\/strong>, Gyorke S, <strong>Zahradnikova A<\/strong> (2005). <a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16260840?dopt=Citation\")'>Calcium activation of ryanodine receptor channels&#8211;reconciling RyR gating models with tetrameric channel structure.<\/a><i> J Gen Physiol.<\/i> 126: 515-527.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/14522820\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-1120\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/AJPCell-113x150.jpg\" alt=\"AJPCell\" width=\"75\" height=\"100\" \/><\/a><\/td>\n<td class=\"two\"><strong>Zahradnikova A<\/strong>, <strong>Kubalova Z<\/strong>, <strong>Pavelkova J<\/strong>, Gyorke S, <strong>Zahradnik I<\/strong> (2004). <a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/14522820\")'>Activation of calcium release assessed by calcium release-induced inactivation of calcium current in rat cardiac myocytes.<\/a><i> Am J Physiol Cell Physiol.<\/i> 286: C330-41.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12839831?dopt=Citation\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-1120\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/AJPCell-113x150.jpg\" alt=\"AJPCell\" width=\"75\" height=\"100\" \/><\/a><\/td>\n<td class=\"two\"><strong>Zahradnikova A<\/strong>, <strong>Dura M<\/strong>, Gyorke I, Escobar AL, <strong>Zahradnik I<\/strong>, Gyorke S (2003). <a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12839831?dopt=Citation\")'>Regulation of dynamic behavior of cardiac ryanodine receptor by Mg2+ under simulated physiological conditions.<\/a><i> Am J Physiol Cell Physiol.<\/i> 285: C1059-1070.<\/td>\n<\/tr>\n<tr>\n<td class=\"small\"><a href='javascript:launchRemote(\"https:\/\/apps.webofknowledge.com\/InboundService.do?product=WOS&#038;SID=S1t42BmuZflkqyZTyXL&#038;UT=WOS%3A000168191300006&#038;SrcApp=EndNote&#038;DestFail=http%3A%2F%2Fwww.webofknowledge.com&#038;action=retrieve&#038;Init=Yes&#038;SrcAuth=ResearchSoft&#038;Func=Frame&#038;customersID=ResearchSoft&#038;IsProductCode=Yes&#038;mode=FullRecord\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-1587 size-full\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/Calcium_Signaling.gif\" alt=\"Calcium_Signaling\" width=\"75\" height=\"90\" \/><\/a><\/td>\n<td class=\"two\"><strong>Zahradnikova A<\/strong>, <strong>Pavelkova J<\/strong>, <strong>Kubalova Z<\/strong>, <strong>Zahradnik I<\/strong>, Gyorke S (2001). <a href='javascript:launchRemote(\"https:\/\/apps.webofknowledge.com\/InboundService.do?product=WOS&#038;SID=S1t42BmuZflkqyZTyXL&#038;UT=WOS%3A000168191300006&#038;SrcApp=EndNote&#038;DestFail=http%3A%2F%2Fwww.webofknowledge.com&#038;action=retrieve&#038;Init=Yes&#038;SrcAuth=ResearchSoft&#038;Func=Frame&#038;customersID=ResearchSoft&#038;IsProductCode=Yes&#038;mode=FullRecord\")'>Simulation of calcium cross-signaling in cardiac cells at the single-channel level.<\/a> In Calcium Signaling. Vol. 331, Ed. M. Morad, P. Kostyuk, IOS Press, Amsterdam, ISB 1-58603-157-0, p.42-51.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"<p>Molekul\u00e1rny mechanizmus v\u00e1pnikovej signaliz\u00e1cie a v\u00e4zba excit\u00e1cie s kontrakciou na srdci &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Nasp\u00e4t Ved\u00faci projektu: Alexandra Zahradn\u00edkov\u00e1 Trvanie: janu\u00e1r 2001 &#8211; december 2005 Koordinuj\u00faca organiz\u00e1cia: \u00dastav&#8230;<span class=\"excerpt_more\"><a href=\"https:\/\/confolab.sav.sk\/ovsb\/projekty\/ukoncene-projekty\/hhmi-55000343\/\">\u010d\u00edta\u0165 \u010falej &raquo;<\/a><\/span><\/p>\n","protected":false},"author":2,"featured_media":0,"parent":117,"menu_order":215,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/449"}],"collection":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/comments?post=449"}],"version-history":[{"count":8,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/449\/revisions"}],"predecessor-version":[{"id":2595,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/449\/revisions\/2595"}],"up":[{"embeddable":true,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/117"}],"wp:attachment":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/media?parent=449"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}