Physiological super-resolution in situ recording reveals kinetic changes of sympathetic norepinephrine release in heart failure

Norepinephrine (NE) in the peripheral nervous system plays crucial roles in regulating peripheral organs in health and disease. However, the spatiotemporal dynamics of sympathetic NE release and its underlying mechanisms remain poorly characterized due to technical challenges. Here, we developed and validated a Slice ElectroChemistry (SEC) method to record sympathetic NE release in heart slices with combined super-resolution and high sensitivity at 1 μm × 1 ms × 1 nM as in patch-clamp recordings. By using the SEC method, we revealed the increased NE release, impaired NE reuptake, increased releasable NE-vesicle pool, and impaired vesicle recycling of sympathetic nerves in the heart of transverse aortic constriction-induced heart failure (HF) mouse model, and defined the increased expression of Cav2.2 calcium channel as a central mechanism mediating the facilitation of NE release and thus the pathogenesis of HF, clarifying a longstanding puzzle about the kinetic changes of cardiac sympathetic NE release in HF. Beyond the heart, SEC enables NE release recording in other peripheral organs and human tissues, providing a robust toolset to investigate sympathetic NE dynamics across diverse pathophysiological conditions.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2026-04-27
DOI
https://doi.org/10.1073/pnas.2519828123
Primary Topic
Cardiac electrophysiology and arrhythmias
Type
article
Field-Weighted Citation Impact
0.00

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article

Physiological super-resolution in situ recording reveals kinetic changes of sympathetic norepinephrine release in heart failure

Jing Lü, Zhuan Zhou, Feipeng Zhu, Lihuan Li et al.
Proceedings of the National Academy of Sciences
Cardiac electrophysiology and arrhythmias
article

Physiological super-resolution in situ recording reveals kinetic changes of sympathetic norepinephrine release in heart failure

Jing Lü, Zhuan Zhou, Feipeng Zhu, Lihuan Li, 郭姝, Changhe Wang, Wei Yao, Jing Yan, Qian Lei, Yu Zhang, Lianghong Zheng, Quanfeng Zhang, Mu Jin, Yun Xiu, Xiaohan Jiang, Tian Li, Jingli Gu, Xianhong Ou, Bing Liu, Xinjiang Kang, Kun Liu, Huadong Xu, Jimin Cao, Bin Liu, Ruiping Xiao, Shirong Wang
article en

Abstract

Norepinephrine (NE) in the peripheral nervous system plays crucial roles in regulating peripheral organs in health and disease. However, the spatiotemporal dynamics of sympathetic NE release and its underlying mechanisms remain poorly characterized due to technical challenges. Here, we developed and validated a Slice ElectroChemistry (SEC) method to record sympathetic NE release in heart slices with combined super-resolution and high sensitivity at 1 μm × 1 ms × 1 nM as in patch-clamp recordings. By using the SEC method, we revealed the increased NE release, impaired NE reuptake, increased releasable NE-vesicle pool, and impaired vesicle recycling of sympathetic nerves in the heart of transverse aortic constriction-induced heart failure (HF) mouse model, and defined the increased expression of Cav2.2 calcium channel as a central mechanism mediating the facilitation of NE release and thus the pathogenesis of HF, clarifying a longstanding puzzle about the kinetic changes of cardiac sympathetic NE release in HF. Beyond the heart, SEC enables NE release recording in other peripheral organs and human tissues, providing a robust toolset to investigate sympathetic NE dynamics across diverse pathophysiological conditions.

Proceedings of the National Academy of SciencesVol. 123(18)
Shandong University (CN), Dalian Medical University (CN), Chinese Academy of Sciences (CN), Peking University (CN), Peking Union Medical College Hospital (CN), King Center (US), Center for Excellence in Brain Science and Intelligence Technology (CN), Beijing Anzhen Hospital (CN), Ministry of Education (PT), Institute of Genetics and Developmental Biology (CN), First Affiliated Hospital of Dalian Medical University (CN), Ministry of Education (TW), Fu Wai Hospital (CN), Capital University of Physical Education and Sports (CN), Jining Medical University (CN), University of Tartu (EE), Xi'an Jiaotong University (CN)
National Natural Science Foundation of China
Good health and well-being
Openalex Percentile: Top 17%
Cardiac electrophysiology and arrhythmias
DOIOpen Access PDFOpenAlex
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