Force relaxation and thin filament protein phosphorylation during acute myocardial ischemia

Young Soo Han, Ozgur Ogut

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Ischemia impairs myocardial function and may contribute to the progression of heart failure. In this study, rats subjected to acute ischemia demonstrated reduced Ca2+-activated force as well as a decrease in myosin-binding protein-C, titin, and Ser23/24 phosphorylation of troponin I (TnI). All three proteins have been demonstrated to be downstream targets of β-adrenergic receptor activation (β-AR), leading to the hypothesis that decreased β-AR signaling during ischemia leads to reduced protein phosphorylation and reduced rate constants of force relaxation. To test this hypothesis, force relaxation transients were recorded from permeabilized perfused and ischemic rat heart fibers following photolysis of the caged chelator diazo-2. Relaxation transients were best fit by double exponential functions whereby the majority (>70%) of the force decline was described by the fast rate constant, which was ~5 times faster than the slow rate constant. However, rate constants of relaxation between perfused and ischemic fibers were not different, despite significant decreases in sarcomeric protein phosphorylation in ischemic fibers. Treatment of perfused fibers with a cAMP analog increased Ser23/24 phosphorylation of TnI, yet the rate constants of relaxation remained unchanged. Interestingly, similar treatment of ischemic fibers did not impact TnI phosphorylation or force relaxation transients. Therefore, acute ischemia does not influence the rate constants of relaxation of permeabilized fibers. These results also suggest that the physiological level of sarcomeric protein phosphorylation is unlikely to be the primary driver of relaxation kinetics in permeabilized cardiac muscle fibers.

Original languageEnglish (US)
Pages (from-to)18-31
Number of pages14
JournalCytoskeleton
Volume68
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Myocardial Ischemia
Phosphorylation
Troponin I
Proteins
Ischemia
Connectin
Photolysis
Chelating Agents
Adrenergic Receptors
Myocardium
Heart Failure

Keywords

  • Heart
  • Ischemia
  • PKA
  • Relaxation
  • Troponin

ASJC Scopus subject areas

  • Cell Biology
  • Structural Biology

Cite this

Force relaxation and thin filament protein phosphorylation during acute myocardial ischemia. / Han, Young Soo; Ogut, Ozgur.

In: Cytoskeleton, Vol. 68, No. 1, 01.2011, p. 18-31.

Research output: Contribution to journalArticle

Han, Young Soo ; Ogut, Ozgur. / Force relaxation and thin filament protein phosphorylation during acute myocardial ischemia. In: Cytoskeleton. 2011 ; Vol. 68, No. 1. pp. 18-31.
@article{2a0d199370274032acda8ab31fe0cd80,
title = "Force relaxation and thin filament protein phosphorylation during acute myocardial ischemia",
abstract = "Ischemia impairs myocardial function and may contribute to the progression of heart failure. In this study, rats subjected to acute ischemia demonstrated reduced Ca2+-activated force as well as a decrease in myosin-binding protein-C, titin, and Ser23/24 phosphorylation of troponin I (TnI). All three proteins have been demonstrated to be downstream targets of β-adrenergic receptor activation (β-AR), leading to the hypothesis that decreased β-AR signaling during ischemia leads to reduced protein phosphorylation and reduced rate constants of force relaxation. To test this hypothesis, force relaxation transients were recorded from permeabilized perfused and ischemic rat heart fibers following photolysis of the caged chelator diazo-2. Relaxation transients were best fit by double exponential functions whereby the majority (>70{\%}) of the force decline was described by the fast rate constant, which was ~5 times faster than the slow rate constant. However, rate constants of relaxation between perfused and ischemic fibers were not different, despite significant decreases in sarcomeric protein phosphorylation in ischemic fibers. Treatment of perfused fibers with a cAMP analog increased Ser23/24 phosphorylation of TnI, yet the rate constants of relaxation remained unchanged. Interestingly, similar treatment of ischemic fibers did not impact TnI phosphorylation or force relaxation transients. Therefore, acute ischemia does not influence the rate constants of relaxation of permeabilized fibers. These results also suggest that the physiological level of sarcomeric protein phosphorylation is unlikely to be the primary driver of relaxation kinetics in permeabilized cardiac muscle fibers.",
keywords = "Heart, Ischemia, PKA, Relaxation, Troponin",
author = "Han, {Young Soo} and Ozgur Ogut",
year = "2011",
month = "1",
doi = "10.1002/cm.20491",
language = "English (US)",
volume = "68",
pages = "18--31",
journal = "Cytoskeleton",
issn = "1949-3584",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Force relaxation and thin filament protein phosphorylation during acute myocardial ischemia

AU - Han, Young Soo

AU - Ogut, Ozgur

PY - 2011/1

Y1 - 2011/1

N2 - Ischemia impairs myocardial function and may contribute to the progression of heart failure. In this study, rats subjected to acute ischemia demonstrated reduced Ca2+-activated force as well as a decrease in myosin-binding protein-C, titin, and Ser23/24 phosphorylation of troponin I (TnI). All three proteins have been demonstrated to be downstream targets of β-adrenergic receptor activation (β-AR), leading to the hypothesis that decreased β-AR signaling during ischemia leads to reduced protein phosphorylation and reduced rate constants of force relaxation. To test this hypothesis, force relaxation transients were recorded from permeabilized perfused and ischemic rat heart fibers following photolysis of the caged chelator diazo-2. Relaxation transients were best fit by double exponential functions whereby the majority (>70%) of the force decline was described by the fast rate constant, which was ~5 times faster than the slow rate constant. However, rate constants of relaxation between perfused and ischemic fibers were not different, despite significant decreases in sarcomeric protein phosphorylation in ischemic fibers. Treatment of perfused fibers with a cAMP analog increased Ser23/24 phosphorylation of TnI, yet the rate constants of relaxation remained unchanged. Interestingly, similar treatment of ischemic fibers did not impact TnI phosphorylation or force relaxation transients. Therefore, acute ischemia does not influence the rate constants of relaxation of permeabilized fibers. These results also suggest that the physiological level of sarcomeric protein phosphorylation is unlikely to be the primary driver of relaxation kinetics in permeabilized cardiac muscle fibers.

AB - Ischemia impairs myocardial function and may contribute to the progression of heart failure. In this study, rats subjected to acute ischemia demonstrated reduced Ca2+-activated force as well as a decrease in myosin-binding protein-C, titin, and Ser23/24 phosphorylation of troponin I (TnI). All three proteins have been demonstrated to be downstream targets of β-adrenergic receptor activation (β-AR), leading to the hypothesis that decreased β-AR signaling during ischemia leads to reduced protein phosphorylation and reduced rate constants of force relaxation. To test this hypothesis, force relaxation transients were recorded from permeabilized perfused and ischemic rat heart fibers following photolysis of the caged chelator diazo-2. Relaxation transients were best fit by double exponential functions whereby the majority (>70%) of the force decline was described by the fast rate constant, which was ~5 times faster than the slow rate constant. However, rate constants of relaxation between perfused and ischemic fibers were not different, despite significant decreases in sarcomeric protein phosphorylation in ischemic fibers. Treatment of perfused fibers with a cAMP analog increased Ser23/24 phosphorylation of TnI, yet the rate constants of relaxation remained unchanged. Interestingly, similar treatment of ischemic fibers did not impact TnI phosphorylation or force relaxation transients. Therefore, acute ischemia does not influence the rate constants of relaxation of permeabilized fibers. These results also suggest that the physiological level of sarcomeric protein phosphorylation is unlikely to be the primary driver of relaxation kinetics in permeabilized cardiac muscle fibers.

KW - Heart

KW - Ischemia

KW - PKA

KW - Relaxation

KW - Troponin

UR - http://www.scopus.com/inward/record.url?scp=78650219273&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650219273&partnerID=8YFLogxK

U2 - 10.1002/cm.20491

DO - 10.1002/cm.20491

M3 - Article

VL - 68

SP - 18

EP - 31

JO - Cytoskeleton

JF - Cytoskeleton

SN - 1949-3584

IS - 1

ER -