title: Ablation of smooth muscle caldesmon affects the relaxation kinetics of arterial muscle.
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 Ca(2+) 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.
authors.affiliation: Boston Biomedical Research Institute, Watertown, MA, 02472, USA.
authors.forename: Hongqiu
authors.initials: H
authors.lastname: Guo
authors.forename: Renjian
authors.initials: R
authors.lastname: Huang
authors.forename: Shingo
authors.initials: S
authors.lastname: Semba
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kordowska
authors.forename: Yang Hoon
authors.initials: YH
authors.lastname: Huh
authors.forename: Yana
authors.initials: Y
authors.lastname: Khalina-Stackpole
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Mabuchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitazawa
authors.forename: Chih-Lueh Albert
authors.initials: CL
authors.lastname: Wang
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002148:Calmodulin-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009126:Muscle Relaxation / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009218:Myosins / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014664:Vasodilation / Q000235:genetics
chemical_list: D002148:Calmodulin-Binding Proteins; D020033:Protein Isoforms; D009218:Myosins