title: Invited Review: pathophysiology of cardiac muscle contraction and relaxation as a result of alterations in thin filament regulation.
abstract: 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 Ca(2+) 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 Ca(2+) sensitivity of force development. This trend in Ca(2+) sensitivity is probably induced by altering the cross-bridge kinetics and the Ca(2+) 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.
authors.affiliation: Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Florida 33136, USA.
authors.forename: O M
authors.initials: OM
authors.lastname: Hernandez
authors.forename: P R
authors.initials: PR
authors.lastname: Housmans
authors.forename: J D
authors.initials: JD
authors.lastname: Potter
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000199:Actins / Q000235:genetics / Q000502:physiology; D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics / Q000503:physiopathology*; D006321:Heart / Q000502:physiology / Q000503:physiopathology*; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology*; D014335:Tropomyosin / Q000235:genetics / Q000502:physiology; D014336:Troponin / Q000235:genetics / Q000502:physiology
chemical_list: D000199:Actins; D014335:Tropomyosin; D014336:Troponin