Physiological super-resolution in situ recording reveals kinetic changes of sympathetic norepinephrine release in heart failure
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (26)
Bing Liu
Xiaohan Jiang
State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology and Peking-Tsinghua Center for Life Sciences and International Data Group/McGovern Institute for Brain Research, Peking University
Shu Guo
Shenzhen Institute for Quantum Science and Engineering, Department of Chemistry, and Department of Physics
Xinjiang Kang
State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology and Peking-Tsinghua Center for Life Sciences and International Data Group/McGovern Institute for Brain Research, Peking University
Jing Lu
Shirong Wang
State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology and Peking-Tsinghua Center for Life Sciences and International Data Group/McGovern Institute for Brain Research, Peking University
Wei Yao
State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology and Peking-Tsinghua Center for Life Sciences and International Data Group/McGovern Institute for Brain Research, Peking University
Xianhong Ou
State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology and Peking-Tsinghua Center for Life Sciences and International Data Group/McGovern Institute for Brain Research, Peking University
Jing Yan
Tian Li
Jingli Gu
State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology and Peking-Tsinghua Center for Life Sciences and International Data Group/McGovern Institute for Brain Research, Peking University
Yun Xiu
State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology and Peking-Tsinghua Center for Life Sciences and International Data Group/McGovern Institute for Brain Research, Peking University
Qian Lei
Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital
Huadong Xu
Department of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University
Mu Jin
State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology and Peking-Tsinghua Center for Life Sciences and International Data Group/McGovern Institute for Brain Research, Peking University
Quanfeng Zhang
State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology and Peking-Tsinghua Center for Life Sciences and International Data Group/McGovern Institute for Brain Research, Peking University
Bin Liu
Lianghong Zheng
State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology and Peking-Tsinghua Center for Life Sciences and International Data Group/McGovern Institute for Brain Research, Peking University
Kun Liu
Feipeng Zhu
State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology and Peking-Tsinghua Center for Life Sciences and International Data Group/McGovern Institute for Brain Research, Peking University
Ruiping Xiao
State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology and Peking-Tsinghua Center for Life Sciences and International Data Group/McGovern Institute for Brain Research, Peking University
Yan Zhang
Changhe Wang
Department of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University
Lihuan Li
Fuwai Hospital and Institute of Basic Medical Science, Peking Union Medical College
Jimin Cao
Institute of Basic Medical Science, Peking Union Medical College
Zhuan Zhou
State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology and Peking-Tsinghua Center for Life Sciences and International Data Group/McGovern Institute for Brain Research, Peking University