Impaired Activity of Ryanodine Receptors Contributes to Calcium Mishandling in Cardiomyocytes of Metabolic Syndrome Rats
Conclusion
Principal findings of this work are that abnormal Ca2+ transient amplitude, contractile dysfunction; and impaired relaxation of MetS cardiomyocytes underlies intrinsic dysfunctional RyR2 and SERCA pump. Abnormal activity of RyRs was evidenced by its decreased ability to bind [3H]-ryanodine. Although the MetS condition does not modify RyR2 protein expression, its phosphorylation at Ser2814 is decreased, which impairs its capacity for activation during ECC. The dysfunctional RyRs, together with a decreased activity of SERCA pump due to decreased Thr17-PLN phosphorylation suggest a downregulation of CaMKII in MetS hearts, though its expression remained unchanged. Dysfunctional RyR2 and SERCA pump participate in the Ca2+ mishandling of MetS cardiomyocytes (i.e., reduced Ca2+ transient amplitude, and decreased Ca2+ spark-mediated Ca2+ leak), may account for the poor overall cardiac outcome reported in MetS patients and could be targeted for future therapies.
Ethics Statement
This study was carried out in accordance with the ethical guidelines of the Mexican Official Norm (NOM-062-ZOO-1999) and the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH publication updated in 2011); and was approved by the Institutional Bioethical Committee for Care and Handling of Laboratory Animals at the CINVESTAV-IPN (approved CICUAL Protocol No. 0105-14).
Author Contributions
GF-M, TR-G, and TB-L contributed to the generation and characterization of ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
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