Molecular actions of drugs that sensitize cardiac myofilaments to Ca2+

Grace M. Arteaga, Tomoyoshi Kobayashi, R. John Solaro

Research output: Contribution to journalReview article

17 Scopus citations

Abstract

Ca2+-sensitizers are inotropic agents that modify the response of myofilaments to Ca2+, and are potentially valuable drugs in the treatment of heart failure. These agents have diverse chemical structures, and in some cases also have effects as inhibitors of phosphodiesterase activity. Advantages of their actions include vasodilation combined with inotropic effects. Reduction in the amounts of Ca2+ required to activate the myofilaments also lowers the oxygen consumption required for Ca2+ transport, lowers the threat of arrhythmias, and may blunt Ca2+-dependent transcriptional and translational mechanisms leading to hypertrophy and failure. Although diastolic abnormalities and impaired relaxation were thought to be potential undesirable effects of Ca2+-sensitizers, studies of hearts beating in situ indicate that this may not be a major problem. We focus here on Ca2+-sensitizers that act on cardiac troponin C, the Ca2+ receptor that triggers activation of the actin-myosin interaction. Structural studies have identified a unique mode of Ca2+ signaling in cardiac troponin C that should aid in targeting drugs to the heart. Moreover, identification of docking sites of Ca2+-sensitizers on troponin C suggest new directions for rational drug design.

Original languageEnglish (US)
Pages (from-to)248-258
Number of pages11
JournalAnnals of Medicine
Volume34
Issue number4
DOIs
StatePublished - Oct 5 2002

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Keywords

  • Ca-sensitizers
  • Heart failure
  • Thin filaments
  • Troponin

ASJC Scopus subject areas

  • Medicine(all)

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