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Nat Commun. 2015 Feb 2;6:6235. doi: 10.1038/ncomms7235.

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

Author information

1
Department of Physiology and Pharmacology, Neuroscience Graduate Program, Oregon Health and Science University, Portland, Oregon 97239, USA.
2
Department of Pharmacology, University of California, Davis, California 95616, USA.
3
Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106, USA.
4
Department of Neurology, Oregon Health and Science University, Portland, Oregon 97239, USA.

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.

PMID:
25639594
PMCID:
PMC4315356
DOI:
10.1038/ncomms7235
[Indexed for MEDLINE]
Free PMC Article
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