Blocking effects of acehytisine on pacemaker currents (If) in sinoatrial node cells and human HCN4 channels expressed in Xenopus laevis oocytes
| Autor: | Junlian Xing, Congxin Huang, Yongjun Chen, Jing Yang, Pan Wu, Xinrong Fan, Jun Zhang, Xi Wang, Hui Chen |
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| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Cardiotonic Agents Patch-Clamp Techniques Potassium Channels Voltage clamp Xenopus Action Potentials Cyclic Nucleotide-Gated Cation Channels Muscle Proteins Biology Heterocyclic Compounds 4 or More Rings Xenopus laevis Acehytisine Pacemaker potential Internal medicine Drug Discovery Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels medicine Animals Humans Patch clamp Cells Cultured Sinoatrial Node Pharmacology Sinoatrial node Rabbit heart Benzazepines Diastolic depolarization biology.organism_classification Cell biology Endocrinology medicine.anatomical_structure Oocytes Female Rabbits Anti-Arrhythmia Agents Drugs Chinese Herbal |
| Zdroj: | Journal of Ethnopharmacology. 139:42-51 |
| ISSN: | 0378-8741 |
| DOI: | 10.1016/j.jep.2011.10.039 |
| Popis: | Ethnopharmacological relevance The root of Aconitum coreanum (Levl.) Raipaics has been extensively used to treat various kinds of disorders including cardiovascular disease in China for a long time. According to recent studies, its antiarrhythmic actions are attributable to the active component, acehytisine. However, the underlying mechanism remains poorly understood. Aim of the study The effects of acehytisine on the spontaneous activity in sinoatrial nodes and the electropharmacological action of this drug on If in pacemaker cells and hHCN4 channels in oocytes were to be investigated. Materials and methods Sinoatrial nodes were cut from rabbit heart, and transmembrane potentials were recorded by standard microelectrode technique. A whole-cell patch clamp technique was employed to record If isolated enzymatically from rabbit sinoatrial node pacemaker cells. Human HCN4 channels were heterologously expressed in Xenopus oocytes and studied using the two-electrode voltage clamp technique. Results Acehytisine decreased the pacemaker rate of firing and slope of diastolic depolarization, modified the action potential configurations and blocked If in rabbit sinoatrial node cells and hHCN4 channels expressed in Xenopus oocytes in a concentration-dependent, voltage-independent and non-use-dependent manner. Its electropharmacological properties were consistent with those of a close-state blocker. Conclusion Our findings are likely to shed light on the clinical application of acehytisine in the treatment of cardiovascular disorders. |
| Databáze: | OpenAIRE |
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