Invited review: Pathophysiology of cardiac muscle contraction and relaxation as a result of alterations in thin filament regulation

Olga M. Hernandez, Philippe R. Housmans, James D. Potter

Research output: Contribution to journalArticle

57 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)1125-1136
Number of pages12
JournalJournal of applied physiology
Volume90
Issue number3
DOIs
StatePublished - Jan 1 2001

Keywords

  • Actin
  • Familial hypertrophic cardiomyopathy
  • Myocardium
  • Tropomyosin
  • Troponin

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Fingerprint Dive into the research topics of 'Invited review: Pathophysiology of cardiac muscle contraction and relaxation as a result of alterations in thin filament regulation'. Together they form a unique fingerprint.

  • Cite this