Cohen I S, Robinson R B
Department of Physiology and Biophysics, Stony Brook University, Room 150 Basic Science Tower, Stony Brook, NY 11794-8661, USA.
Handb Exp Pharmacol. 2006(171):41-71. doi: 10.1007/3-540-29715-4_2.
The ionic basis of automaticity in the sinoatrial node and His-Purkinje system, the primary and secondary cardiac pacemaking regions, is discussed. Consideration is given to potential targets for pharmacologic or genetic therapies of rhythm disorders. An ideal target would be an ion channel that functions only during diastole, so that action potential repolarization is not affected, and one that exhibits regional differences in expression and/or function so that the primary and secondary pacemakers can be selectively targeted. The so-called pacemaker current, If, generated by the HCN gene family, best fits these criteria. The biophysical and molecular characteristics of this current are reviewed, and progress to date in developing selective pharmacologic agents targeting If and in using gene and cell-based therapies to modulate the current are reviewed.
本文讨论了心脏主要和次要起搏区域——窦房结和希氏-浦肯野系统中自律性的离子基础。文中还考虑了针对节律紊乱的药物或基因治疗的潜在靶点。理想的靶点应该是一种仅在舒张期起作用的离子通道，这样动作电位复极化就不会受到影响，并且该通道在表达和/或功能上表现出区域差异，以便能够选择性地靶向主要和次要起搏器。由HCN基因家族产生的所谓起搏电流If最符合这些标准。本文回顾了该电流的生物物理和分子特征，以及迄今为止在开发靶向If的选择性药物制剂以及使用基于基因和细胞的疗法来调节该电流方面所取得的进展。
