Document Detail


Ablation of smooth muscle caldesmon affects the relaxation kinetics of arterial muscle.
MedLine Citation:
PMID:  23149489     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
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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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-11-14
Journal Detail:
Title:  Pflügers Archiv : European journal of physiology     Volume:  465     ISSN:  1432-2013     ISO Abbreviation:  Pflugers Arch.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-01     Completed Date:  2013-07-17     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  283-94     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Arteries / metabolism,  pathology,  physiopathology
Calmodulin-Binding Proteins / genetics*,  metabolism
Homozygote
Kinetics
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscle Relaxation / genetics*
Muscle, Smooth, Vascular / metabolism*,  pathology,  physiopathology
Myosins / metabolism
Phosphorylation
Protein Isoforms / genetics,  metabolism
Up-Regulation
Vasodilation / genetics
Grant Support
ID/Acronym/Agency:
P01 AR041637/AR/NIAMS NIH HHS; P01-AM41637/AM/NIADDK NIH HHS; R01 HL092252/HL/NHLBI NIH HHS; R01-HL92252/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Calmodulin-Binding Proteins; 0/Protein Isoforms; EC 3.6.4.1/Myosins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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