Sartiani Laura, Romanelli Maria Novella, Mugelli Alessandro, Cerbai Elisabetta
Department of NeuroFarBa, C.I.M.M.B.A., University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy.
Curr Drug Targets. 2015;16(8):868-76. doi: 10.2174/1389450116666150531152047.
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.
超极化激活的环核苷酸门控（HCN）通道在心脏窦房结细胞和未成熟心肌细胞的起搏活动产生中起重要作用。HCN通道也存在于成人心房和心室心肌细胞中，其生理作用目前正在研究中。在不同的心脏疾病中，功能失调的HCN通道被认为是心律失常的直接原因。虽然HCN通道功能丧失突变与窦性心动过缓有关，但房颤、心室肥厚和衰竭中HCN通道功能获得可能有助于增强异位电活动并促进心律失常的发生。伊伐布雷定是目前可用于临床的选择性心动过缓药物，用其阻断HCN通道可改善心脏功能，并对抗实验性肥厚中的功能重塑。因此，伊伐布雷定可改善慢性心力衰竭患者的临床结局。对心脏HCN通道亚型具有更高选择性的新型化合物正在作为新药开发的潜在候选物进行研究。
