Akademik Veri Yönetim Sistemi
Cardiovascular Research, cilt.89, sa.3, ss.634-642, 2011 (SCI-Expanded)
AimsZinc exists in biological systems as bound and histochemically reactive free Zn2+. It is an essential structural constituent of many proteins, including enzymes from cellular signalling pathways, in which it functions as a signalling molecule. In cardiomyocytes at rest, Zn2+ concentration is in the nanomolar range. Very little is known about precise mechanisms controlling the intracellular distribution of Zn2+ and its variations during cardiac function.Methods and resultsLive-cell detection of intracellular Zn2+ has become feasible through the recent development of Zn2+-sensitive and selective fluorophores able to distinguish Zn2+ from Ca2+. Here, in freshly isolated rat cardiomyocytes, we investigated the rapid changes in Zn2+ homeostasis using the Zn2+-specific fluorescent dye, FluoZin-3, in comparison to Ca2+-dependent fluo-3 fluorescence. Zn2+ sparks and Zn2 transients, in quiescent and electrically stimulated cardiomyocytes, respectively, were visualized in a similar manner to known rapid Ca2 changes. Both Zn2+ sparks and Zn2+ transients required Ca2+ entry. Inhibiting the sarcoplasmic reticulum Ca2 release or increasing the Ca2+ load in a low-Na + solution suppressed or increased Zn2 movements, respectively. Mitochondrial inhibitors slightly reduced both Zn2 sparks and Zn2+ transients. Oxidation by H2+O2+ facilitated and acidic pH inhibited the Ca2+-dependent Zn 2+ release.ConclusionIt is proposed that Zn2+ release during the cardiac cycle results mostly from intracellular free Ca2+ increase, triggering production of reactive oxygen species that induce changes in metal-binding properties of metallothioneins and other redox-active proteins, aside from ionic exchange on these proteins. © 2010 The Author.