Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Editorial
. 2015 May 8;116(10):1639-42.
doi: 10.1161/CIRCRESAHA.115.306439.

Adrenergic and cholinergic plasticity in heart failure

Stanley F Fernandez  1 , John M Canty Jr  2
Affiliations
Editorial

Adrenergic and cholinergic plasticity in heart failure

Stanley F Fernandez et al. Circ Res. .
No abstract available

Keywords: Editorials; adrenergic agents; heart failure; muscarinic agents; sudden death.

PubMed Disclaimer

Figures

Figure
Figure. Cholinergic remodeling in heart failure
The Figure summarizes the plasticity of neurotransmitters in the sympathetic nerve ganglion in conjunction with postsynaptic receptors on cardiac myocytes. In the normal heart (Panel A), myocardial sympathetic nerves originating in the stellate ganglion secrete norepinephrine (NE, red) to increase heart rate and myocardial contractility through β1-adrenergic receptor signaling. The interstitial NE level at the receptor is dependent upon release as well as the presynaptic reuptake (Uptake 1) mechanism for recycling it into the presynaptic terminal. Parasympathetic control of ventricular contractility (not illustrated) is generally felt to play a minor role. In heart failure (Panel B), plasticity of neurons in the sympathetic ganglia leads to transdifferentiation of some cell bodies to a cholinergic phenotype (blue). Some sympathetic nerves now express Choline Acetyltransferase (AChAT) and tyrosine hydroxylase (TH) expression decreases. This transdifferentiation is promoted by Leukemia Inhibitory Factor (LIF), Cardiotrophin-1 expression and Nerve Growth Factor (NGF) released from the myocardium. Reductions in NE reuptake as well as increased circulating NE levels elevate interstitial NE and lead to post-synaptic down regulation of β1 receptor density, uncoupling of β1 receptors with G proteins and desensitization of β adrenergic signaling. In heart failure, cardiomyocytes paradoxically increase the expression of muscarinic (M2) receptors. The result of cholinergic transdifferentiation of sympathetic neurons and the upregulation of M2 muscarinic receptors leads to diminished beta adrenergic responses and could paradoxically potentiate cholinergic myocardial responses (paradoxic bradycardia and reduced contractility) during sympathetic nerve activation. ACh: Acetylcholine, NET: Norepinephrine transporter.
Figure
Figure. Cholinergic remodeling in heart failure
The Figure summarizes the plasticity of neurotransmitters in the sympathetic nerve ganglion in conjunction with postsynaptic receptors on cardiac myocytes. In the normal heart (Panel A), myocardial sympathetic nerves originating in the stellate ganglion secrete norepinephrine (NE, red) to increase heart rate and myocardial contractility through β1-adrenergic receptor signaling. The interstitial NE level at the receptor is dependent upon release as well as the presynaptic reuptake (Uptake 1) mechanism for recycling it into the presynaptic terminal. Parasympathetic control of ventricular contractility (not illustrated) is generally felt to play a minor role. In heart failure (Panel B), plasticity of neurons in the sympathetic ganglia leads to transdifferentiation of some cell bodies to a cholinergic phenotype (blue). Some sympathetic nerves now express Choline Acetyltransferase (AChAT) and tyrosine hydroxylase (TH) expression decreases. This transdifferentiation is promoted by Leukemia Inhibitory Factor (LIF), Cardiotrophin-1 expression and Nerve Growth Factor (NGF) released from the myocardium. Reductions in NE reuptake as well as increased circulating NE levels elevate interstitial NE and lead to post-synaptic down regulation of β1 receptor density, uncoupling of β1 receptors with G proteins and desensitization of β adrenergic signaling. In heart failure, cardiomyocytes paradoxically increase the expression of muscarinic (M2) receptors. The result of cholinergic transdifferentiation of sympathetic neurons and the upregulation of M2 muscarinic receptors leads to diminished beta adrenergic responses and could paradoxically potentiate cholinergic myocardial responses (paradoxic bradycardia and reduced contractility) during sympathetic nerve activation. ACh: Acetylcholine, NET: Norepinephrine transporter.
See this image and copyright information in PMC

Comment on

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Cao JM, Fishbein MC, Han JB, Lai WW, Lai AC, Wu TJ, Czer L, Wolf PL, Denton TA, Shintaku IP, Chen PS, Chen LS. Relationship between regional cardiac hyperinnervation and ventricular arrhythmia. Circulation. 2000;101:1960–1969. - PubMed
    1. Canty JM, Jr, Suzuki G, Banas MD, Verheyen F, Borgers M, Fallavollita JA. Hibernating myocardium: Chronically adapted to ischemia but vulnerable to sudden death. Circ Res. 2004;94:1142–1149. - PubMed
    1. Han S, Kobayashi K, Joung B, Piccirillo G, Maruyama M, Vinters HV, March K, Lin SF, Shen C, Fishbein MC, Chen PS, Chen LS. Electroanatomic remodeling of the left stellate ganglion after myocardial infarction. J Am Coll Cardiol. 2012;59:954–61. - PMC - PubMed
    1. Fernandez SF, Ovchinnikov V, Canty JM, Jr, Fallavollita JA. Hibernating myocardium results in partial sympathetic denervation and nerve sprouting. Am J Physiol Heart Circ Physiol. 2013;304:H318–27. - PMC - PubMed
    1. Fallavollita JA, Heavey BM, Luisi J AJ, Michalek SM, Baldwa S, Mashtare J TL, Hutson AD, deKemp RA, Haka MS, Sajjad M, Cimato TR, Curtis AB, Cain ME, Canty J JM. Regional myocardial sympathetic denervation predicts the risk of sudden cardiac arrest in ischemic cardiomyopathy. J Am Coll Cardiol. 2014;63:141–149. - PMC - PubMed