{"id":17943,"date":"2025-09-03T10:50:12","date_gmt":"2025-09-03T08:50:12","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=news&#038;p=17943"},"modified":"2025-09-03T10:50:39","modified_gmt":"2025-09-03T08:50:39","slug":"blebbistatin-reduces-calcium-buffering-in-cardiomyocytes","status":"publish","type":"news","link":"https:\/\/nanion.com\/ja\/news\/blebbistatin-reduces-calcium-buffering-in-cardiomyocytes\/","title":{"rendered":"Blebbistatin reduces calcium buffering in cardiomyocytes"},"content":{"rendered":"<p>Intracellular calcium (Ca\u00b2\u207a) buffering is essential for cardiac excitation\u2013contraction (EC) coupling and electrophysiological stability. In cardiomyocytes, ~99% of Ca\u00b2\u207a is bound to buffers\u2014primarily myofilaments\u2014leaving only a small fraction free to regulate signaling. Even modest changes in buffering affinity can disrupt Ca\u00b2\u207a homeostasis and promote arrhythmogenic remodeling.<\/p>\n<p>In a new study published, researchers from the University Medical Center G\u00f6ttingen and the German Center for Cardiovascular Research (DZHK), examined the effects of blebbistatin (a myosin II ATPase inhibitor commonly used to uncouple contraction) on calcium buffering and ion channel function in human iPSC-derived atrial cardiomyocytes (iPSC-aCM).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Key findings:<\/strong><\/p>\n<ul>\n<li><strong>Reduced buffer affinity<\/strong>: Blebbistatin (10 \u03bcmol\/L) increased the buffer dissociation constant (K<sub>d<\/sub>), indicating lower Ca\u00b2\u207a binding affinity. The maximum buffering capacity (B<sub>max<\/sub>) remained unchanged.<\/li>\n<li><strong>Elevated free Ca\u00b2\u207a<\/strong>: Treated cells showed significantly higher diastolic and systolic Ca\u00b2\u207a levels, increased sarcoplasmic reticulum (SR) Ca\u00b2\u207a leak, and more frequent spontaneous Ca\u00b2\u207a release events (sparks).<\/li>\n<li><strong>Electrophysiological changes<\/strong>: Peak I<sub>Na<\/sub> and I<sub>Ca,L<\/sub> densities were unaffected, but I<sub>Ca,L<\/sub> inactivation kinetics were faster, and I<sub>K1<\/sub> density was reduced.<\/li>\n<li><strong>Reversibility<\/strong>: All changes were abolished by intracellular Ca\u00b2\u207a chelation with EGTA, confirming that effects were secondary to altered buffering.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3><\/h3>\n<p>This study highlights intracellular Ca\u00b2\u207a buffering as a modifiable target in arrhythmia research. Blebbistatin-induced desensitization of Ca\u00b2\u207a buffers mimics pathological conditions seen in atrial fibrillation and cardiomyopathy. The reversibility of these effects with EGTA suggests that pharmacological modulation of Ca\u00b2\u207a buffering (either through sensitizers or chelators) could be a viable strategy for anti-arrhythmic therapy development.<\/p>\n<p>Moreover, blebbistatin incubation may serve as a\u00a0model system for screening compounds that restore Ca\u00b2\u207a homeostasis, offering a translational bridge between cellular mechanisms and therapeutic innovation.<\/p>\n<p data-start=\"2598\" data-end=\"2946\">&#8212;&#8211;<\/p>\n<p data-start=\"2953\" data-end=\"3116\">\ud83d\udcd6 Read the full article: <a href=\"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP287545\" target=\"_blank\" rel=\"noopener\">Blebbistatin reduces calcium buffering in cardiomyocytes: Consequences for cellular electrophysiology (Journal of Physiology, 2025)<\/a><\/p>\n<p data-start=\"2953\" data-end=\"3116\">Learn more about the <a href=\"\/products\/syncropatch-384\/\" target=\"_blank\" rel=\"noopener\">SyncroPatch 384<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Intracellular calcium (Ca\u00b2\u207a) buffering is essential for cardiac excitation\u2013contraction (EC) coupling and elect [&hellip;]<\/p>\n","protected":false},"featured_media":17945,"template":"","news_categories":[528,15],"class_list":["post-17943","news","type-news","status-publish","has-post-thumbnail","hentry","news_categories-front-page-news","news_categories-blogs"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/news\/17943","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/news"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/news"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media\/17945"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=17943"}],"wp:term":[{"taxonomy":"news_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/news_categories?post=17943"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}