Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, 141, rue de la cardonille, 34094, Montpellier, France.
LabEx Ion Channels Science and Therapeutics (ICST), Montpellier, France.
Pflugers Arch. 2020 Jul;472(7):817-830. doi: 10.1007/s00424-020-02421-1. Epub 2020 Jun 29.
The heart automaticity is a fundamental physiological function in vertebrates. The cardiac impulse is generated in the sinus node by a specialized population of spontaneously active myocytes known as "pacemaker cells." Failure in generating or conducting spontaneous activity induces dysfunction in cardiac automaticity. Several families of ion channels are involved in the generation and regulation of the heart automaticity. Among those, voltage-gated L-type Cav1.3 (α1D) and T-type Cav3.1 (α1G) Ca channels play important roles in the spontaneous activity of pacemaker cells. Ca channel channelopathies specifically affecting cardiac automaticity are considered rare. Recent research on familial disease has identified mutations in the Cav1.3-encoding CACNA1D gene that underlie congenital sinus node dysfunction and deafness (OMIM # 614896). In addition, both Cav1.3 and Cav3.1 channels have been identified as pathophysiological targets of sinus node dysfunction and heart block, caused by congenital autoimmune disease of the cardiac conduction system. The discovery of channelopathies linked to Cav1.3 and Cav3.1 channels underscores the importance of Ca channels in the generation and regulation of heart's automaticity.
心脏自律性是脊椎动物的基本生理功能。心脏冲动由窦房结中的特殊自主活性心肌细胞（称为“起搏细胞”）产生。自发活动的产生或传导功能障碍会导致心脏自律性障碍。有几种离子通道家族参与了心脏自律性的产生和调节。其中，电压门控 L 型 Cav1.3（α1D）和 T 型 Cav3.1（α1G）钙通道在起搏细胞的自发活动中发挥重要作用。专门影响心脏自律性的钙通道病被认为很少见。最近对家族性疾病的研究发现，CACNA1D 基因（编码 Cav1.3）的突变是先天性窦房结功能障碍和耳聋（OMIM#614896）的基础。此外，Cav1.3 和 Cav3.1 通道已被确定为先天性自身免疫性心脏传导系统疾病引起的窦房结功能障碍和心脏传导阻滞的病理生理学靶点。与 Cav1.3 和 Cav3.1 通道相关的通道病的发现强调了钙通道在心脏自律性的产生和调节中的重要性。
