Chinese natural compound decreases pacemaking of rabbit cardiac sinoatrial cells by targeting second messenger regulation of f-channels

Author:

Piantoni Chiara1ORCID,Paina Manuel1ORCID,Molla David1ORCID,Liu Sheng2ORCID,Bertoli Giorgia1ORCID,Jiang Hongmei2ORCID,Wang Yanyan3ORCID,Wang Yi4ORCID,Wang Yi5ORCID,DiFrancesco Dario1ORCID,Barbuti Andrea1ORCID,Bucchi Annalisa1ORCID,Baruscotti Mirko1ORCID

Affiliation:

1. Department of Biosciences, The Cell Physiology Lab and “Centro Interuniversitario di Medicina Molecolare e Biofisica Applicata”, Università degli Studi di Milano

2. Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University

3. School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine

4. College of Pharmaceutical Sciences, Zhejiang University

5. Institute of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine

Abstract

Tongmai Yangxin (TMYX) is a complex compound of the Traditional Chinese Medicine (TCM) used to treat several cardiac rhythm disorders; however, no information regarding its mechanism of action is available. In this study we provide a detailed characterization of the effects of TMYX on the electrical activity of pacemaker cells and unravel its mechanism of action. Single-cell electrophysiology revealed that TMYX elicits a reversible and dose-dependent (2/6 mg/ml) slowing of spontaneous action potentials rate (−20.8/–50.2%) by a selective reduction of the diastolic phase (−50.1/–76.0%). This action is mediated by a negative shift of the If activation curve (−6.7/–11.9 mV) and is caused by a reduction of the cyclic adenosine monophosphate (cAMP)-induced stimulation of pacemaker channels. We provide evidence that TMYX acts by directly antagonizing the cAMP-induced allosteric modulation of the pacemaker channels. Noticeably, this mechanism functionally resembles the pharmacological actions of muscarinic stimulation or β-blockers, but it does not require generalized changes in cytoplasmic cAMP levels thus ensuring a selective action on rate. In agreement with a competitive inhibition mechanism, TMYX exerts its maximal antagonistic action at submaximal cAMP concentrations and then progressively becomes less effective thus ensuring a full contribution of If to pacemaker rate during high metabolic demand and sympathetic stimulation.

Funder

Le Ren Tang

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3