Reduced force production during low blood flow to the heart correlates with altered troponin i phosphorylation

Bridgette Christopher, Gresin O. Pizarro, Bryson Nicholson, Samantha Yuen, Brian D. Hoit, Ozgur Ogut

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

A rat model of low myocardial blood flow was established to test the hypothesis that post-translational changes to proteins of the thin and thick muscle filaments correlate with decreased cardiac contractility. Following 3 days of low blood flow by constriction of the left anterior descending artery, rat hearts demonstrated a reduction in fractional shortening at rest and a relative decline in fractional shortening when challenged with high dose versus low dose dobutamine, reflecting reduced energy reserves. Permeabilized fibers from low blood flow hearts demonstrated a decline in maximum force per cross-section and Ca2+ sensitivity as compared to their sham operated counterparts. An examination of sarcomeric proteins by twodimensional gel electrophoresis, mass spectrometry, and phospho-specific antibodies provided evidence for Ser23/24 and Ser43/45 phosphorylation of troponin I (TnI). Total TnI phosphorylation was not different between the groups, but Ser23/24 phosphorylation declined with low blood flow, implying an accompanying increase in phosphorylation at other sites of TnI. Affinity chromatography demonstrated that TnI from low blood flow myocardium had reduced relative affinity to Ca 2+ bound troponin C compared to TnI from sham operated hearts, providing a mechanism for reduced Ca2+ sensitivity of force production in low blood flow fibers. These findings suggest that altered TnI function, due to changes in the distribution of phosphorylated sites, is an early contributor to reduced contractility of the heart.

Original languageEnglish (US)
Pages (from-to)111-123
Number of pages13
JournalJournal of Muscle Research and Cell Motility
Volume30
Issue number3-4
DOIs
StatePublished - Jun 2009

Keywords

  • Force
  • Myosin
  • Phosphorylation
  • Troponin

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cell Biology

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