Altered interactions among thin filament proteins modulate cardiac function

R. John Solaro, Jennifer Van Eyk

Research output: Contribution to journalReview article

Abstract

The transition of cardiac muscle myofilament activity from the diastolic to the systolic state is a complex allosteric/co-operative process, rich in potential control mechanisms. The rate and intensity of the transition is modulated by the mechanical state of the myofilaments, by covalent and non-covalent mechanisms, and by the isoform population of myofilament proteins. Moreover, the process is altered in pathological states and subject to modification by pharmacological agents with potential use as inotropic drugs. We present here a current perception of the process, with focus on molecular interactions of the thin filament components, especially troponin I. Our discussion is couched in terms of what eve believe to be pressing questions in the current state of knowledge of this system. These questions are as follows: what is the topology of the thin filament and how do thin filament proteins regulate the activation of cross-bridge cycling? What is the relative role of protein phosphorylation of thin filament proteins in the regulation of the cardiac activity and dynamics? What is the relative role of feedback effects of cross-bridge binding on thin filament activity? Answers to these questions have taken on new significance, with the identification of familial hypertrophic cardiomyopathy as a 'sarcomeric' disease related to missense mutations in myosin, troponin T, and tropomyosin. As discussed, new and exciting developments in this area are bringing us closer to the answers to these questions.

Original languageEnglish (US)
Pages (from-to)217-230
Number of pages14
JournalJournal of Molecular and Cellular Cardiology
Volume28
Issue number2
DOIs
StatePublished - Feb 1996

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Keywords

  • Actin
  • Inotropic agents
  • Ischemia
  • Length-dependent activation
  • Phosphorylation
  • Tropomyosin
  • roponin

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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