Targeting protein tyrosine phosphatase σ after myocardial infarction restores cardiac sympathetic innervation and prevents arrhythmias

R. T. Gardner, L. Wang, B. T. Lang, J. M. Cregg, C. L. Dunbar, William Woodward, J. Silver, C. M. Ripplinger, Beth Habecker

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Millions of people suffer a myocardial infarction (MI) every year, and those who survive have increased risk of arrhythmias and sudden cardiac death. Recent clinical studies have identified sympathetic denervation as a predictor of increased arrhythmia susceptibility. Chondroitin sulfate proteoglycans present in the cardiac scar after MI prevent sympathetic reinnervation by binding the neuronal protein tyrosine phosphatase receptor σ (PTPσ). Here we show that the absence of PTPσ, or pharmacologic modulation of PTPσ by the novel intracellular sigma peptide (ISP) beginning 3 days after injury, restores sympathetic innervation to the scar and markedly reduces arrhythmia susceptibility. Using optical mapping we observe increased dispersion of action potential duration, supersensitivity to β-adrenergic receptor stimulation and Ca 2+ mishandling following MI. Sympathetic reinnervation prevents these changes and renders hearts remarkably resistant to induced arrhythmias.

Original languageEnglish (US)
Article number6235
JournalNature Communications
Volume6
DOIs
StatePublished - 2015

Fingerprint

myocardial infarction
arrhythmia
Protein Tyrosine Phosphatases
phosphatases
tyrosine
Cardiac Arrhythmias
Myocardial Infarction
proteins
scars
Cicatrix
Chondroitin Sulfate Proteoglycans
adrenergics
magnetic permeability
Adrenergic Receptors
Sympathectomy
Sudden Cardiac Death
stimulation
Modulation
death
Action Potentials

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Targeting protein tyrosine phosphatase σ after myocardial infarction restores cardiac sympathetic innervation and prevents arrhythmias. / Gardner, R. T.; Wang, L.; Lang, B. T.; Cregg, J. M.; Dunbar, C. L.; Woodward, William; Silver, J.; Ripplinger, C. M.; Habecker, Beth.

In: Nature Communications, Vol. 6, 6235, 2015.

Research output: Contribution to journalArticle

Gardner, R. T. ; Wang, L. ; Lang, B. T. ; Cregg, J. M. ; Dunbar, C. L. ; Woodward, William ; Silver, J. ; Ripplinger, C. M. ; Habecker, Beth. / Targeting protein tyrosine phosphatase σ after myocardial infarction restores cardiac sympathetic innervation and prevents arrhythmias. In: Nature Communications. 2015 ; Vol. 6.
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AU - Woodward, William

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