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

Author

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  • R. T. Gardner

    (Neuroscience Graduate Program, Oregon Health and Science University)

  • L. Wang

    (University of California)

  • B. T. Lang

    (Case Western Reserve University)

  • J. M. Cregg

    (Case Western Reserve University)

  • C. L. Dunbar

    (Neuroscience Graduate Program, Oregon Health and Science University)

  • W. R. Woodward

    (Oregon Health and Science University)

  • J. Silver

    (Case Western Reserve University)

  • C. M. Ripplinger

    (University of California)

  • B. A. Habecker

    (Neuroscience Graduate Program, Oregon Health and Science University)

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 Ca2+ mishandling following MI. Sympathetic reinnervation prevents these changes and renders hearts remarkably resistant to induced arrhythmias.

Suggested Citation

  • R. T. Gardner & L. Wang & B. T. Lang & J. M. Cregg & C. L. Dunbar & W. R. Woodward & J. Silver & C. M. Ripplinger & B. A. Habecker, 2015. "Targeting protein tyrosine phosphatase σ after myocardial infarction restores cardiac sympathetic innervation and prevents arrhythmias," Nature Communications, Nature, vol. 6(1), pages 1-9, May.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7235
    DOI: 10.1038/ncomms7235
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    Cited by:

    1. Renjie Qiu & Xingying Zhang & Chen Song & Kaige Xu & Huijia Nong & Yi Li & Xianglong Xing & Kibret Mequanint & Qian Liu & Quan Yuan & Xiaomin Sun & Malcolm Xing & Leyu Wang, 2024. "E-cardiac patch to sense and repair infarcted myocardium," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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