Abstract
Spinophilin (SPN) is a ubiquitously expressed scaffolding protein that interacts through several binding modules with a variety of target proteins. Thus, SPN bundles F-actin, targets protein phosphatase 1 to the ryanodine receptor, and targets regulators of G-protein signaling to G-protein coupled receptors in cardiomyocytes. In this work we studied the role of SPN on cardiomyocyte morphology, function, and β-adrenergic responsiveness using a homozygous SPN knock-out mouse model (SPN−/−). We show that spinophilin deficiency significantly (1) reduced cardiomyocyte length, (2) increases both Ca2+ amplitude and maximal rate of Ca2+ rise during systole, and (3) decreased shortening amplitude and maximal rate of shortening, while (4) β-adrenergic stimulation remained intact. Our data suggest that spinophilin is an upstream regulator required for normal growth and excitation–contraction coupling, but is dispensable for β-adrenergic stimulation of adult cardiomyocytes.
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Acknowledgments
We thank Petra Sakel (MDC, Berlin, Germany) for technical assistance and for preparing the primary adult cardiomyocytes. We thank Wolfgang-Peter Schlegel for technical support of the single cell experiments.
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Petzhold, D., da Costa-Goncalves, A.C., Gross, V. et al. Spinophilin is required for normal morphology, Ca2+ homeostasis and contraction but dispensable for β-adrenergic stimulation of adult cardiomyocytes. J Muscle Res Cell Motil 32, 243–248 (2011). https://doi.org/10.1007/s10974-011-9259-4
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DOI: https://doi.org/10.1007/s10974-011-9259-4