Moroni A, Gorza L, Beltrame M, Gravante B, Vaccari T, Bianchi M E, Altomare C, Longhi R, Heurteaux C, Vitadello M, Malgaroli A, DiFrancesco D
Dipartimento di Fisiologia e Biochimica Generali, Università degli Studi di Milano, via Celoria 26, Milano 20133, Italy.
J Biol Chem. 2001 Aug 3;276(31):29233-41. doi: 10.1074/jbc.M100830200. Epub 2001 Apr 27.
The pacemaker current I(f) of the sinoatrial node (SAN) is a major determinant of cardiac diastolic depolarization and plays a key role in controlling heart rate and its modulation by neurotransmitters. Substantial expression of two different mRNAs (HCN4, HCN1) of the family of pacemaker channels (HCN) is found in rabbit SAN, suggesting that the native channels may be formed by different isoforms. Here we report the cloning and heterologous expression of HCN1 from rabbit SAN and its specific localization in pacemaker myocytes. rbHCN1 is an 822-amino acid protein that, in human embryonic kidney 293 cells, displayed electrophysiological properties similar to those of I(f), suggesting that HCN1 can form a pacemaker channel. The presence of HCN1 in the SAN myocytes but not in nearby heart regions, and the electrophysiological properties of the channels formed by it, suggest that HCN1 plays a central and specific role in the formation of SAN pacemaker currents.
窦房结（SAN）的起搏电流I(f)是心脏舒张期去极化的主要决定因素，在控制心率及其受神经递质调节方面发挥关键作用。在兔窦房结中发现了起搏通道（HCN）家族的两种不同mRNA（HCN4、HCN1）的大量表达，这表明天然通道可能由不同的亚型构成。在此，我们报告了兔窦房结HCN1的克隆、异源表达及其在起搏心肌细胞中的特异性定位。rbHCN1是一种含822个氨基酸的蛋白质，在人胚肾293细胞中表现出与I(f)相似的电生理特性，这表明HCN1可形成起搏通道。HCN1存在于窦房结心肌细胞而非附近的心脏区域，且由其形成的通道具有电生理特性，这表明HCN1在窦房结起搏电流的形成中发挥着核心且特定的作用。
