摘要
超极化活性核苷酸循环渠道在心脏窦房结细胞和不成熟的心肌细胞起搏活动的传递中发挥重要作用。HCN通道也存在于成人心房和心室心肌细胞,当前其生理作用正在研究中。已经提出,在不同的心脏疾病,HCN通道功能失调是心率失常的直接原因。虽然HCN通道功能损失突变与窦性心动过缓有关,HCN通道在房颤、心室肥大和心衰的正常功能可能促进了异位电活动、促进心律失常。 利用ivabradine 来阻塞HCN通道,是目前临床使用的一种选择性减慢心率的药物,可改善心脏性能和抵消功能性重构。因此,ivabradine可以改善慢性心力衰竭患者的症状。目前,正在研究开发新颖的、选择性强的心脏HCN亚型通道的药物。
关键词: 心率失常,房室结,心肌肥大,心肌细胞,HCN通道,窦房结
Current Drug Targets
Title:Updates on HCN Channels in the Heart: Function, Dysfunction and Pharmacology
Volume: 16 Issue: 8
Author(s): Laura Sartiani, Maria Novella Romanelli, Alessandro Mugelli and Elisabetta Cerbai
Affiliation:
关键词: 心率失常,房室结,心肌肥大,心肌细胞,HCN通道,窦房结
摘要: The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play an important role in the generation of pacemaker activity of cardiac sinoatrial node cells and immature cardiomyocytes. HCN channels are also present in adult atrial and ventricular cardiomyocytes, where the physiological role is currently under investigation. In different cardiac pathologies, dysfunctional HCN channels have been suggested to be a direct cause of rhythm disorders. While loss-of-function mutations of HCN channels are associated with sinus bradycardia, HCN channel gain-of-function in atrial fibrillation, ventricular hypertrophy and failure might help enhance ectopic electrical activity and promote arrhythmogenesis. Blockade of HCN channels with ivabradine, a selective bradycardic agent currently available for clinical use, improves cardiac performance and counteracts functional remodeling in experimental hypertrophy. Accordingly, ivabradine ameliorates clinical outcome in patients with chronic heart failure. Novel compounds with enhanced selectivity for cardiac HCN channel isoforms are being studied as potential candidates for new drug development.
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Laura Sartiani, Maria Novella Romanelli, Alessandro Mugelli and Elisabetta Cerbai , Updates on HCN Channels in the Heart: Function, Dysfunction and Pharmacology, Current Drug Targets 2015; 16 (8) . https://dx.doi.org/10.2174/1389450116666150531152047
DOI https://dx.doi.org/10.2174/1389450116666150531152047 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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