{"id":445,"date":"2018-01-10T12:30:13","date_gmt":"2018-01-10T12:30:13","guid":{"rendered":"http:\/\/confolab.sav.sk\/ovsb\/?page_id=445"},"modified":"2023-10-06T14:05:40","modified_gmt":"2023-10-06T14:05:40","slug":"nih-firca-ro3-tw005543-1","status":"publish","type":"page","link":"https:\/\/confolab.sav.sk\/ovsb\/projekty\/ukoncene-projekty\/nih-firca-ro3-tw005543-1\/","title":{"rendered":"NIH FIRCA RO3 TW005543\/1"},"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>V\u00e1pnikov\u00e1 signaliz\u00e1cia v srdcovej v\u00e4zbe excit\u00e1cie s kontrakciou &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<button onclick=\"goBack()\">Nasp\u00e4\u0165<\/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: Sandor Gyorke, Texas Tech University, Lubbock, TX, USA<br \/>\nMedzin\u00e1rodn\u00fd spolupracovn\u00edk: <a href=\"https:\/\/confolab.sav.sk\/ovsb\/pracovnici\/vyskumnici\/ing-alexandra-zahradnikova-drsc\/\">Alexandra Zahradn\u00edkov\u00e1<\/a>, <a href=\"https:\/\/confolab.sav.sk\/ovsb\/pracovnici\/vyskumnici\/rndr-ivan-zahradnik-csc\/\">Ivan Zahradn\u00edk<\/a><\/h3>\n<h3>Trvanie: marec 2001 &#8211; august 2004<br \/>\nKoordinuj\u00faca organiz\u00e1cia: Texas Tech University, Lubbock, TX, USA<\/h3>\n<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Anot\u00e1cia:<\/span><\/h3>\n<p>V\u00e4zba excit\u00e1cie s kontrakciou (ECC) v cicav\u010dom srdcovom svale je sprostredkovan\u00e1 v\u00e1pnikovou signaliz\u00e1ciou v tubulo-retikul\u00e1rnej \u0161trbinu. To zah\u0155\u0148a s\u00e9riu molekul\u00e1rnych dejov: nap\u00e4\u0165ovo-z\u00e1visl\u00fa aktiv\u00e1ciu plazmatick\u00fdch Ca2+ kan\u00e1lov L-typu (DHPR); dif\u00faziu a v\u00e4zbu Ca2+ i\u00f3nov v tubulo-retikul\u00e1rnej \u0161trbine; Ca2+-z\u00e1visl\u00fa aktiv\u00e1ciu ryanod\u00ednov\u00e9ho receptora (RyR) v termin\u00e1lnej cisterne; uvo\u013e\u0148ovanie Ca2+ i\u00f3nov do tubulo-retikul\u00e1rnej \u0161trbiny; amplifik\u00e1ciu uvo\u013e\u0148ovania v\u00e1pnika prostredn\u00edctvom Ca2+-z\u00e1vislej aktiv\u00e1cie susediacich RyR kan\u00e1lov, a inhib\u00edciu v\u00e1pnikov\u00e9ho pr\u00fadu prostredn\u00edctvom Ca2+-z\u00e1vislej inaktiv\u00e1cie DHPR kan\u00e1lov. \u017diaden z tieto stochastick\u00fdch dejov nie je dostato\u010dne objasnen\u00fd. Nie je jasn\u00e9, ako sa tieto procesy podie\u013eaj\u00fa na efekt\u00edvnosti v\u00e4zby excit\u00e1cie s kontrakciou a grad\u00e1cii uvo\u013e\u0148ovania v\u00e1pnika podnetom. Na\u0161ou hlavnou hypot\u00e9zou je, \u017ee \u0161pecifick\u00e9 vlastnosti ECC v srdcov\u00fdch myocytoch s\u00fa d\u00f4sledkom \u0161pecifickej mikroarchitekt\u00fary tubulo-retikul\u00e1rneho spojenia, skladaj\u00faceho sa z klastrov DHPR a RyR kan\u00e1lov, ktor\u00e9 maj\u00fa \u0161pecifick\u00e9 vr\u00e1tkovacie vlastnosti z\u00e1visl\u00e9 od koncentr\u00e1cie v\u00e1pnika. T\u00fato hypot\u00e9zu sme rozpracovali do predstavy jednotky v\u00e4zby excit\u00e1cie s kontrakciou (ECCU). Rozumieme \u0148ou v\u0161etky kan\u00e1ly srdcovej diadickej \u0161trbiny, definovan\u00e9 svojimi vodivostn\u00fdmi a vr\u00e1tkovac\u00edmi vlastnos\u0165ami, vz\u00e1jomn\u00fdm topologick\u00fdm usporiadan\u00edm a i\u00f3nov\u00fdm prostred\u00edm. DHPR kan\u00e1ly tvoria excita\u010dn\u00fa jednotku \u2013 podmno\u017einu ECCU, v ktorej ako odpove\u010f na nap\u00e4\u0165ov\u00fd podnet vznikaj\u00fa v\u00e1pnikov\u00e9 pr\u00fady. RyR kan\u00e1ly tvoria v\u00e1pnik uvo\u013e\u0148uj\u00facu jednotku \u2013 podmno\u017einu ECCU, v ktorej vznikaj\u00fa element\u00e1rne udalosti uvo\u013e\u0148ovania v\u00e1pnika (v\u00e1pnikov\u00e9 z\u00e1blesky\/hroty).<\/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 svalov\u00e9 bunky, v\u00e4zba excit\u00e1cie s kontrakciou<\/td>\n<\/tr>\n<tr>\n<td>\n<h3><span class=\"H3\">Ciele:<\/span><\/h3>\n<p>Cie\u013eom tohto projektu je definova\u0165 k\u013e\u00fa\u010dov\u00e9 kroky riadenia uvo\u013e\u0148ovania v\u00e1pnika excit\u00e1ciou na \u00farovni v\u00e1pnikovej signaliz\u00e1cie medzi jednotliv\u00fdmi kan\u00e1lmi tvoriacimi diadick\u00fa ECC jednotku, a ur\u010di\u0165 ich fyziologick\u00fd v\u00fdznam. Na dosiahnutie tohto cie\u013ea vyu\u017eijeme p\u00f4vodn\u00fd model kinetiky v\u00e1pnikov\u00e9ho pr\u00fadu s inaktiv\u00e1ciou z\u00e1vislou na uvo\u013e\u0148ovan\u00ed v\u00e1pnika a p\u00f4vodn\u00fd program na simul\u00e1ciu elektrofyziologick\u00fdch experimentov, zalo\u017een\u00fd na simul\u00e1ci\u00ed vz\u00e1jomne sa ovplyv\u0148uj\u00facich klastrov kan\u00e1lov, oba vyvinut\u00e9 na slovenskom pracovisku. S\u00fastred\u00edme sa koncentrova\u0165 na tri \u00fazko s\u00favisiace \u0161pecifick\u00e9 ciele. 1. Definova\u0165 mechanizmus v\u00e1pnikovej signaliz\u00e1cie v ECCU po\u010das aktiv\u00e1cie v\u00e1pnikov\u00e9ho uvo\u013e\u0148ovania. Z\u00e1merom t\u00fdchto pokusov je zisti\u0165 usporiadanie ECCU a ur\u010di\u0165, ktor\u00e9 kroky pozit\u00edvnej sp\u00e4tnej v\u00e4zby v\u00e1pnikovej signaliz\u00e1cie v ECCU s\u00fa d\u00f4le\u017eit\u00e9 pre efekt\u00edvnos\u0165 a spo\u013eahlivos\u0165 v\u00e1pnikom indukovan\u00e9ho uvo\u013enenia v\u00e1pnika (CICR). 2. Ur\u010di\u0165 mechanizmus inaktiv\u00e1cie DHPR uvo\u013enen\u00fdmi Ca2+ i\u00f3nmi a definova\u0165 jej fyziologick\u00fd v\u00fdznam. Z\u00e1merom t\u00fdchto experimentov je ur\u010di\u0165 mechanizmus negat\u00edvnej sp\u00e4tnej v\u00e4zby v\u00e1pnikovej signaliz\u00e1cie v ECCU, d\u00f4le\u017eitych pre efekt\u00edvnos\u0165 a stabilitu CICR. 3. Definova\u0165 k\u013e\u00fa\u010dov\u00e9 kroky, riadiace zosilenenie a efekt\u00edvnos\u0165 ECCU s d\u00f4razom na grad\u00e1ciu E-C v\u00e4zby na \u00farovni kardiomyocytu. Predpoklad\u00e1me, \u017ee nap\u00e4\u0165ov\u00e1 a \u010dasov\u00e1 z\u00e1vislos\u0165 zmeny vnutrobunkovej koncentr\u00e1cie Ca2+, a teda aj kontrakcia, s\u00fa v\u00fdsledkom sum\u00e1cie stochasticky rozlo\u017een\u00fdch odpoved\u00ed jednotliv\u00fdch ECCU na podnet.<\/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\/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\/14535832?dopt=Citation\")'><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-1120\" src=\"https:\/\/www.biomed.cas.cz\/physiolres\/img\/S5_2015.jpg\" alt=\"AJPCell\" width=\"75\" height=\"100\" \/><\/a><\/td>\n<td class=\"two\"><strong>Dura M<\/strong>, <strong>Zahradnik I<\/strong>, <strong>Zahradnikova A<\/strong> (2003): <a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/14535832?dopt=Citation\")'>Kinetics of cardiac RyR channel gating studied at high temporal resolution.<\/a><i> Physiol Res.<\/i> 52: 571-578.<\/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<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"<p>V\u00e1pnikov\u00e1 signaliz\u00e1cia v srdcovej v\u00e4zbe excit\u00e1cie s kontrakciou &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Nasp\u00e4\u0165 Ved\u00faci projektu: Sandor Gyorke, Texas Tech University, Lubbock, TX, USA Medzin\u00e1rodn\u00fd spolupracovn\u00edk: Alexandra Zahradn\u00edkov\u00e1, Ivan Zahradn\u00edk&#8230;<span class=\"excerpt_more\"><a href=\"https:\/\/confolab.sav.sk\/ovsb\/projekty\/ukoncene-projekty\/nih-firca-ro3-tw005543-1\/\">\u010d\u00edta\u0165 \u010falej &raquo;<\/a><\/span><\/p>\n","protected":false},"author":2,"featured_media":0,"parent":117,"menu_order":210,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/445"}],"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=445"}],"version-history":[{"count":4,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/445\/revisions"}],"predecessor-version":[{"id":2594,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/445\/revisions\/2594"}],"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=445"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}