The Acute Effects of Leptin on the Contractility of Isolated Rat Atrial and Ventricular Cardiomyocytes
| Autor: | Anastasia Khokhlova, Tatiana Myachina, Xenia Butova, Anastasia Kochurova, Ekaterina Polyakova, Michael Galagudza, Olga Solovyova, Galina Kopylova, Daniil Shchepkin |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Leptin
Sarcomeres Myocardium Organic Chemistry General Medicine Myosins Myocardial Contraction Catalysis Computer Science Applications Rats Inorganic Chemistry leptin atria ventricles single cardiomyocytes sarcomere shortening calcium transients actin–myosin interaction protein phosphorylation Animals Calcium Myocytes Cardiac Physical and Theoretical Chemistry Molecular Biology Spectroscopy |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 15; Pages: 8356 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms23158356 |
| Popis: | Leptin is a pleiotropic peptide playing an important role in the regulation of cardiac functions. It is not clear whether leptin directly modulates the mechanical function of atrial cardiomyocytes. We compared the acute effects of leptin on the characteristics of mechanically non-loaded sarcomere shortening and cytosolic Ca2+ concentration ([Ca2+]i) transients in single rat atrial and ventricular cardiomyocytes. We also studied the functional properties of myosin obtained from cardiomyocytes using an in vitro motility assay and assessed the sarcomeric protein phosphorylation. Single cardiomyocytes were exposed to 5, 20, and 60 nM leptin for 60 min. In ventricular cardiomyocytes, 60 nM leptin depressed sarcomere shortening amplitude and decreased the rates of shortening and relaxation. These effects were accompanied by a decrease in the phosphorylation of cMyBP-C, an increase in Tpm phosphorylation, and a slowdown of the sliding velocity of thin filaments over myosin in the in vitro motility assay. In contrast, in atrial cardiomyocytes, the phosphorylation of cMyBP-C and TnI increased, and the characteristics of sarcomere shortening did not change. Leptin had no effect on the characteristics of [Ca2+]i transients in ventricular cardiomyocytes, while 5 nM leptin prolonged [Ca2+]i transients in atrial cardiomyocytes. Thus, leptin-induced changes in contractility of ventricular cardiomyocytes may be attributed to the direct effects of leptin on cross-bridge kinetics and sarcomeric protein properties rather than changes in [Ca2+]i. We also suggest that the observed differences between atrial and ventricular cardiomyocytes may be associated with the peculiarities of the expression of leptin receptors, as well as signaling pathways in the atrial and ventricular myocardium. |
| Databáze: | OpenAIRE |
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