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Ablation of smooth muscle caldesmon affects the relaxation kinetics of arterial muscle

  • Muscle physiology
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Abstract

Smooth muscle caldesmon (h-CaD) is an actin- and myosin-binding protein that reversibly inhibits the actomyosin ATPase activity in vitro. To test the function of h-CaD in vivo, we eliminated its expression in mice. The h-CaD-null animals appeared normal and fertile, although the litter size was smaller. Tissues from the homozygotes lacked h-CaD and exhibited upregulation of the non-muscle isoform, l-CaD, in visceral, but not vascular tonic smooth muscles. While the Ca2+ sensitivity of force generation of h-CaD-deficient smooth muscle remained largely unchanged, the kinetic behavior during relaxation in arteries was different. Both intact and permeabilized arterial smooth muscle tissues from the knockout animals relaxed more slowly than those of the wild type. Since this difference occurred after myosin dephosphorylation was complete, the kinetic effect most likely resulted from slower detachment of unphosphorylated crossbridges. Detailed analyses revealed that the apparently slower relaxation of h-CaD-null smooth muscle was due to an increase in the amplitude of a slower component of the biphasic tension decay. While the identity of this slower process has not been unequivocally determined, we propose it reflects a thin filament state that elicits fewer re-attached crossbridges. Our finding that h-CaD modulates the rate of smooth muscle relaxation clearly supports a role in the control of vascular tone.

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Acknowledgments

This work was supported by grants from NIH (P01-AM41637 and R01-HL92252). The authors wish to thank Dr. Hiroshi Mashimo for his assistance in the early phase of this project and Dr. Lynne Coluccio for reading the manuscript.

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  1. Boston Biomedical Research Institute, 64 Grove St, Watertown, MA, 02472, USA

    Hongqiu Guo, Renjian Huang, Shingo Semba, Jolanta Kordowska, Yang Hoon Huh, Yana Khalina-Stackpole, Katsuhide Mabuchi, Toshio Kitazawa & Chih-Lueh Albert Wang

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  1. Hongqiu Guo
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Guo, H., Huang, R., Semba, S. et al. Ablation of smooth muscle caldesmon affects the relaxation kinetics of arterial muscle. Pflugers Arch - Eur J Physiol 465, 283–294 (2013). https://doi.org/10.1007/s00424-012-1178-8

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