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Review
. 2016 Feb;9(2):e001359.
doi: 10.1161/CIRCEP.115.001359.

Molecular Mechanisms of Sympathetic Remodeling and Arrhythmias

Ryan T Gardner  1 , Crystal M Ripplinger  1 , Rachel C Myles  1 , Beth A Habecker  2
Affiliations
Review

Molecular Mechanisms of Sympathetic Remodeling and Arrhythmias

Ryan T Gardner et al. Circ Arrhythm Electrophysiol. 2016 Feb.
No abstract available

Keywords: electrophysiology; myocardial infarction; norepinephrine; receptors, adrenergic; sympathetic nervous system.

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Conflict of interest statement

Conflict of Interest Disclosures: None

Figures

Figure 1
Figure 1
Hyperinnervation and denervation can both contribute to arrhythmias. Acute hyperinnervation or excess NE (Top) leads to increased activation of β-ARs (beta adrenergic receptors) and subsequent changes in Ik and calcium overload. β-AR signaling increases Ik which shortens action potential duration (APD). At the same time, intracellular Ca2+ rises due to enhanced influx via the L-type Ca2+ channel and increased release from the sarcoplasmic reticulum (SR). Extrusion of Ca2+ from the cytosol via the Na+/Ca2+ exchanger (NCX) produces a net inward current leading to delayed afterdepolarizations (DADs). In contrast, chronic hyperinnervation leads to desensitization of β-AR signaling and decreased Ik. Chronic denervation (Bottom) results in β-AR supersensitivity and decreased Ito. Activation of super-sensitive β-AR signaling pathways by circulating epinephrine leads to calcium overload and DADs.
Figure 2
Figure 2
Neurotrophins stimulate different effects in sympathetic neurons via activation of p75NTR and/or TrkA. Pro-Neurotrophins like ProNGF and ProBDNF are processed to mature neurotrophins (NGF, BDNF) by intra- and extra-cellular proteases. Activation of a p75NTR/Sortilin receptor complex by ProNGF or ProBDNF, or activation of p75NTR by BDNF, stimulates axon degeneration in sympathetic neurons. In contrast, NGF signaling via TrkA or a TrkA/p75NTR receptor complex stimulates sympathetic axon maintenance and growth.
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