Aim: To explore whether the differential effects of Zn2+ on ryanodine binding to the sarcoplasmic reticulum (SR) of skeletal and cardiac muscles resulted from different permeability of the SR to Zn2+.
Methods: [3H]ryanodine binding assays were performed to examine the effect of Zn2+ on ryanodine binding to the SR in the presence of pyrithione sodium (PyNa), a specific Zn2+ ionophore.
Results: As a control, PyNa up to 50 micromol/L did not induce any effect on ryanodine binding to the SR of cardiac muscle. But PyNa 1-100 micromol/L increased ryanodine binding in skeletal muscle with maximum binding (222.2+/-20.9 % of the control) and inhibited ryanodine binding to 50 % of the control at about 500 micromol/L. In the presence of PyNa 10 and 50 micromol/L the dose-dependence of the effect of Zn2+ in cardiac muscle was still monophasic and not changed by PyNa, while the biphasic effect of Zn2+ in skeletal muscle became monophasic.
Conclusion: Different permeability of the SR to Zn2+ may account for the differential effects of Zn2+ on ryanodine binding in skeletal and cardiac muscles. PyNa is not a strictly specific Zn2+ ionophore.
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PLoS One
January 2025
Department of Pathology, 906 Hospital of Joint Logistic Support Force of PLA, Ningbo, Zhejiang, China.
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PLoS One
January 2025
Department of Entomology and Acarology, Luiz de Queiroz College of Agriculture (ESALQ), University of São Paulo (USP), Piracicaba, São Paulo, Brazil.
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Department of General Biology, Biological Sciences Center, State University of Londrina - UEL, Londrina, Paraná, Brazil. Electronic address:
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December 2024
Cardiac Signaling Center, University of South Carolina, Medical University of South Carolina and Clemson University, Charleston, SC 29425, USA.
Over 200 point mutations in the ryanodine receptor (RyR2) of the cardiac sarcoplasmic reticulum (SR) are known to be associated with cardiac arrhythmia. We have already reported on the calcium signaling phenotype of a point mutation in RyR2 Ca binding site Q3925E expressed in human stem-cell-derived cardiomyocytes (hiPSC-CMs) that was found to be lethal in a 9-year-old girl. CRISPR/Cas9-gene-edited mutant cardiomyocytes carrying the RyR2-Q3925E mutation exhibited a loss of calcium-induced calcium release (CICR) and caffeine-triggered calcium release but continued to beat arrhythmically without generating significant SR Ca release, consistent with a remodeling of the calcium signaling pathway.
View Article and Find Full Text PDFHum Genomics
January 2025
Division of Genome Science, Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Chungbuk, 28159, Republic of Korea.
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