Myocardial infarction causes transient cholinergic transdifferentiation of cardiac sympathetic nerves via gp130

Antoinette Olivas, Ryan T. Gardner, Lianguo Wang, Crystal M. Ripplinger, William Woodward, Beth Habecker

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Sympathetic and parasympathetic control of the heart is a classic example of norepinephrine (NE) and acetylcholine (ACh) triggering opposing actions. Sympathetic NE increases heart rate and contractility through activation of β receptors, whereas parasympathetic ACh slows the heart through muscarinic receptors. Sympathetic neurons can undergo a developmental transition from production of NE to ACh and we provide evidence that mouse cardiac sympathetic nerves transiently produce ACh after myocardial infarction (MI). ACh levels increased in viable heart tissue 10–14 d after MI, returning to control levels at 21 d, whereas NE levels were stable. At the same time, the genes required for ACh synthesis increased in stellate ganglia, which contain most of the sympathetic neurons projecting to the heart. Immunohistochemistry 14 d after MI revealed choline acetyltransferase (ChAT) in stellate sympathetic neurons and vesicular ACh transporter immunoreactivity in tyrosine hydroxylase-positive cardiac sympathetic fibers. Finally, selective deletion of the ChAT gene from adult sympathetic neurons prevented the infarction-induced increase in cardiac ACh. Deletion of the gp130 cytokine receptor from sympathetic neurons prevented the induction of cholinergic genes after MI, suggesting that inflammatory cytokines induce the transient acquisition of a cholinergic phenotype in cardiac sympathetic neurons. Ex vivo experiments examining the effect of NE and ACh on rabbit cardiac action potential duration revealed that ACh blunted both the NE-stimulated decrease in cardiac action potential duration and increase in myocyte calcium transients. This raises the possibility that sympathetic co-release of ACh and NE may impair adaptation to high heart rates and increase arrhythmia susceptibility.

Original languageEnglish (US)
Pages (from-to)479-488
Number of pages10
JournalJournal of Neuroscience
Volume36
Issue number2
DOIs
StatePublished - Jan 13 2016

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Cholinergic Agents
Acetylcholine
Myocardial Infarction
Norepinephrine
Neurons
Choline O-Acetyltransferase
Action Potentials
Cytokine Receptor gp130
Vesicular Acetylcholine Transport Proteins
Heart Rate
Genes
Stellate Ganglion
Myocardial Contraction
Adrenergic Fibers
Tyrosine 3-Monooxygenase
Muscarinic Receptors
Muscle Cells
Infarction
Cardiac Arrhythmias
Immunohistochemistry

Keywords

  • Cholinergic
  • Cytokine
  • Myocardial infarction
  • Sympathetic
  • Transdifferentiation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Myocardial infarction causes transient cholinergic transdifferentiation of cardiac sympathetic nerves via gp130. / Olivas, Antoinette; Gardner, Ryan T.; Wang, Lianguo; Ripplinger, Crystal M.; Woodward, William; Habecker, Beth.

In: Journal of Neuroscience, Vol. 36, No. 2, 13.01.2016, p. 479-488.

Research output: Contribution to journalArticle

Olivas, Antoinette ; Gardner, Ryan T. ; Wang, Lianguo ; Ripplinger, Crystal M. ; Woodward, William ; Habecker, Beth. / Myocardial infarction causes transient cholinergic transdifferentiation of cardiac sympathetic nerves via gp130. In: Journal of Neuroscience. 2016 ; Vol. 36, No. 2. pp. 479-488.
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