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

التفاصيل البيبلوغرافية
العنوان: Chinese natural compound decreases pacemaking of rabbit cardiac sinoatrial cells by targeting second messenger regulation of f-channels
المؤلفون: Chiara Piantoni, Manuel Paina, David Molla, Sheng Liu, Giorgia Bertoli, Hongmei Jiang, Yanyan Wang, Yi Wang, Dario DiFrancesco, Andrea Barbuti, Annalisa Bucchi, Mirko Baruscotti
المصدر: eLife, Vol 11 (2022)
بيانات النشر: eLife Sciences Publications Ltd, 2022.
سنة النشر: 2022
المجموعة: LCC:Medicine
LCC:Science
LCC:Biology (General)
مصطلحات موضوعية: pacemaker current, sinoatrial node, TMYX, pure bradycardic agents, cAMP antagonism, HCN channels, Medicine, Science, Biology (General), QH301-705.5
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2050-084X
Relation: https://elifesciences.org/articles/75119; https://doaj.org/toc/2050-084X
DOI: 10.7554/eLife.75119
URL الوصول: https://doaj.org/article/5a4c42db53c340f6bcf8c080de7fbe1a
رقم الأكسشن: edsdoj.5a4c42db53c340f6bcf8c080de7fbe1a
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2050084X
DOI:10.7554/eLife.75119