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, W. R. Woodward, J. Silver, C. M. Ripplinger () and B. A. Habecker ()
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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

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7235

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