{"id":442,"date":"2018-01-10T12:24:41","date_gmt":"2018-01-10T12:24:41","guid":{"rendered":"http:\/\/confolab.sav.sk\/ovsb\/?page_id=442"},"modified":"2023-10-06T14:02:30","modified_gmt":"2023-10-06T14:02:30","slug":"nih-firca-ro3-tw005543-2","status":"publish","type":"page","link":"https:\/\/confolab.sav.sk\/ovsb\/projekty\/ukoncene-projekty\/nih-firca-ro3-tw005543-2\/","title":{"rendered":"NIH FIRCA RO3 TW005543\/2"},"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>Reorganiz\u00e1cia v\u00e1pnikovej signaliz\u00e1cie v zlyh\u00e1vaj\u00facom srdci &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, Ohio State University, Columbus, OH, 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: m\u00e1j 2005 &#8211; apr\u00edl 2008<br \/>\nKoordinuj\u00faca organiz\u00e1cia: Ohio State University, Columbus, OH, 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 \u0161trbine. Na\u0161ou z\u00e1kladnou hypot\u00e9zou je, \u017ee mikroarchitekt\u00fara tubulo-retikul\u00e1rnej \u0161trbiny, tvoren\u00e1 aponovan\u00fdmi klastrami DHPR a RyR kan\u00e1lov, vyzna\u010duj\u00facimi sa \u0161pecifick\u00fdmi, od v\u00e1pnika z\u00e1visl\u00fdmi vr\u00e1tkovac\u00edmi vlastnos\u0165ami, je zodpovedn\u00e1 za jedine\u010dn\u00e9 vlastnosti ECC srdcov\u00fdch myocytov. T\u00e1to hypot\u00e9zu vy\u00fastila do koncepcie jednotky v\u00e4zby excit\u00e1cie s kontrakciou (ECCU). Pod ECCU rozumieme konkr\u00e9tnu \u0161trukt\u00faru &#8211; srdcov\u00fa di\u00e1du &#8211; s do nej patriacou mno\u017einou i\u00f3nov\u00fdch kan\u00e1lov a \u010fal\u0161\u00edch prote\u00ednov. V prvom pribl\u00ed\u017een\u00ed ECCU pozost\u00e1va z excita\u010dnej jednotky (EU), reprezentovanej segmentom plazmatickej membr\u00e1ny s klastrom DHPR kan\u00e1lov, a z v\u00e1pnik uvo\u013e\u0148uj\u00facej jednotky (RU) reprezentovanej segmentom membr\u00e1ny SR s klastrom RyR kan\u00e1lov. I\u00f3nov\u00e9 kan\u00e1ly s\u00fa ur\u010den\u00e9 svojimi vodivostn\u00fdmi a vr\u00e1tkovac\u00edmi vlastnos\u0165ami, topologick\u00fdm usporiadan\u00edm a i\u00f3nov\u00fdm prostred\u00edm. Cie\u013eom predlo\u017een\u00e9ho projektu je definova\u0165 \u00falohu zmien v mikroarchitekt\u00fare srdcov\u00fdch buniek, t.j. v ich bunkovej distrib\u00facii, morfol\u00f3gii a topologick\u00fdch vlastnostiach, v zhor\u0161en\u00ed efekt\u00edvnosti uvo\u013e\u0148ovania v\u00e1pnika uvo\u013enenia po\u010das zlyh\u00e1vania srdca. Na dosiahnutie tohto cie\u013ea pou\u017eijeme viacer\u00e9 p\u00f4vodn\u00e9 met\u00f3dy vyvinut\u00e9 na slovenskom pracovisku, t.j. model kinetiky v\u00e1pnikov\u00e9ho pr\u00fadu s inaktiv\u00e1ciou z\u00e1vislou od uvo\u013enenia v\u00e1pnika, program na simul\u00e1ciu elektrofyziologick\u00e9ho experimentu, zalo\u017een\u00fd na simul\u00e1cii vz\u00e1jomne sa ovplyv\u0148uj\u00facich klastrov kan\u00e1lov, a techniku selekt\u00edvneho vyvolania inaktiv\u00e1cie v\u00e1pnikov\u00e9ho pr\u00fadu z\u00e1vislej od uvo\u013enenia v\u00e1pnika.<\/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>Tento v\u00fdskum bude prim\u00e1rne vykon\u00e1van\u00fd na Slovensku ako NIH grant #HL074045. Celkov\u00fdm cie\u013eom tohto projektu je objasni\u0165 zmeny mechanizmov v\u00e1pnikovej signaliz\u00e1cie v di\u00e1dach cicav\u010d\u00edch srdcov\u00fdch svalov\u00fdch buniek po\u010das zlyh\u00e1vania srdca. Di\u00e1dy pozost\u00e1vaj\u00fa z klastrov tvoren\u00fdch v\u00e1pnikov\u00fdmi kan\u00e1lmi L-typu (DHPR) v apoz\u00edci\u00ed s klastrami ryanod\u00ednov\u00fdch receptorov, navz\u00e1jom funk\u010dne prepojen\u00fdch prostredn\u00edctvom i\u00f3nov v\u00e1pnika. Zmeny vo v\u00e1pnikovej signaliz\u00e1cii po\u010das v\u00e4zby excit\u00e1cie s kontrakciou prispievaj\u00fa k poklesu v\u00fdkonu zlyh\u00e1vaj\u00faceho srdca. Ur\u010d\u00edme rozsah zmien jednotliv\u00fdch krokov v\u00e1pnikovej signaliz\u00e1cie po\u010das aktiv\u00e1cie uvo\u013e\u0148ovania v\u00e1pnika z DHPR a ich vz\u0165ah k ultra\u0161truktur\u00e1lnej organiz\u00e1ci\u00ed di\u00e1d a k topol\u00f3gii kan\u00e1lov v element\u00e1rnych jednotk\u00e1ch E-C v\u00e4zby. Za t\u00fdmto \u00fa\u010delom zmeriame kinetiku v\u00e1pnikov\u00fdch pr\u00fadov a zmien koncentr\u00e1cie vn\u00fatrobunkov\u00e9ho v\u00e1pnika v srdcov\u00fdch myocytoch, ako aj element\u00e1rnych udalost\u00ed uvo\u013e\u0148ovania v\u00e1pnika (tzv. v\u00e1pnikov\u00e9 hroty). Tieto merania bud\u00fa doplnen\u00e9 morfologickou anal\u00fdzou objemovej a povrchovej hustoty tubul\u00e1rneho syst\u00e9mu a cisterien a pozd\u013a\u017eneho sarkoplazmatick\u00e9ho retikula a anal\u00fdzou kolokaliz\u00e1cie v\u00e1pnikov\u00fdch kan\u00e1lov a v\u00e1pnik uvo\u013e\u0148uj\u00facich kan\u00e1lov pomocou elektr\u00f3novej a konfok\u00e1lnej mikroskopie. Kvantitat\u00edvnou anal\u00fdzou kinetiky v\u00e1pnikov\u00e9ho pr\u00fadu a kinetiky uvo\u013e\u0148ovania v\u00e1pnika aby sme ur\u010d\u00edme parametre v\u00e1pnikovej signaliz\u00e1cie rozhoduj\u00face pre riadenie grad\u00e1cie a efekt\u00edvnosti v\u00e4zby excit\u00e1cie s kontrakciou. Na ur\u010denie mo\u017en\u00fdch mechanizmov a dizajn experimentov s vysokou v\u00fdpovednou hodnotou pou\u017eijeme po\u010d\u00edta\u010dov\u00fa simul\u00e1ciu experimentov. Pochopenie abnormal\u00edt srdcovej E-C v\u00e4zby v zlyh\u00e1vaj\u00facom srdci je d\u00f4le\u017eit\u00e9, preto\u017ee tento proces m\u00f4\u017ee by\u0165 vhodn\u00fdm strategick\u00fdm cie\u013eom terapeutickej intervencie. Definovanie vz\u0165ahu medzi priestorov\u00fdm usporiadan\u00edm klastrov kan\u00e1lov a ich v\u00e1pnikovej signaliz\u00e1cie m\u00e1 navy\u0161e \u0161ir\u0161\u00ed v\u00fdznam pre pochopenie procesov, ak\u00fdmi s\u00fa napr\u00edklad synaptick\u00fd prenos, neuroendokrinn\u00e1 sekr\u00e9cia a regul\u00e1cia cievneho tonusu.<\/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\/18591191\")'><img decoding=\"async\" class=\"alignnone wp-image-1118\" src=\"https:\/\/confolab.sav.sk\/ovsb\/wp-content\/uploads\/JPhysiol.jpg\" alt=\"JPhysiol\" width=\"75\" \/><\/a><\/td>\n<td class=\"two\"><strong>Polakova E<\/strong>,<strong> Zahradnikova A Jr<\/strong>, <strong>Pavelkova J<\/strong>, <strong>Zahradnik I<\/strong>, <strong>Zahradnikova A<\/strong> (2008). <a href='javascript:launchRemote(\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18591191\")'>Local calcium release activation by DHPR calcium channel openings in rat cardiac myocytes.<\/a><i> J Physiol.<\/i> 586: 3839-3854.<\/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\/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(\"https:\/\/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<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"<p>Reorganiz\u00e1cia v\u00e1pnikovej signaliz\u00e1cie v zlyh\u00e1vaj\u00facom srdci &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Nasp\u00e4\u0165 Ved\u00faci projektu: Sandor Gyorke, Ohio State University, Columbus, OH, USA Medzin\u00e1rodn\u00fd spolupracovn\u00edk: Alexandra Zahradn\u00edkov\u00e1, Ivan Zahradn\u00edk Trvanie: m\u00e1j&#8230;<span class=\"excerpt_more\"><a href=\"https:\/\/confolab.sav.sk\/ovsb\/projekty\/ukoncene-projekty\/nih-firca-ro3-tw005543-2\/\">\u010d\u00edta\u0165 \u010falej &raquo;<\/a><\/span><\/p>\n","protected":false},"author":2,"featured_media":0,"parent":117,"menu_order":205,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/442"}],"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=442"}],"version-history":[{"count":4,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/442\/revisions"}],"predecessor-version":[{"id":2592,"href":"https:\/\/confolab.sav.sk\/ovsb\/wp-json\/wp\/v2\/pages\/442\/revisions\/2592"}],"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=442"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}