Plasticity in skeletal cardiac, and smooth muscle -: Invited review:: Pathophysiology of cardiac muscle contraction and relaxation as a result of alterations in thin filament regulation

被引:58
作者
Hernandez, OM
Housmans, PR
Potter, JD
机构
[1] Univ Miami, Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA
[2] Mayo Clin & Mayo Fdn, Dept Anesthesiol, Rochester, MN 55905 USA
关键词
familial hypertrophic cardiomyopathy; troponin; tropomyosin; actin; myocardium;
D O I
10.1152/jappl.2001.90.3.1125
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Cardiac muscle contraction depends on the tightly regulated interactions of thin and thick filament proteins of the contractile apparatus. Mutations of thin filament proteins (actin, tropomyosin, and troponin), causing familial hypertrophic cardiomyopathy (FHC), occur predominantly in evolutionarily conserved regions and induce various functional defects that impair the normal contractile mechanism. Dysfunctional properties observed with the FHC mutants include altered Ca2+ sensitivity, changes in ATPase activity, changes in the force and velocity of contraction, and destabilization of the contractile complex. One apparent tendency observed in these thin filament mutations is an increase in the Ca2+ sensitivity of force development. This trend in Ca2+ sensitivity is probably induced by altering the cross-bridge kinetics and the Ca2+ affinity of troponin C. These in vitro defects lead to a wide variety of in vivo cardiac abnormalities and phenotypes, some more severe than others and some resulting in sudden cardiac death.
引用
收藏
页码:1125 / 1136
页数:12
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