Wu M H, Su M J, Lue H C
Department of Pediatrics, National Taiwan University, Taipei, Republic of China.
J Mol Cell Cardiol. 1994 Sep;26(9):1167-77. doi: 10.1006/jmcc.1994.1135.
Age-related cardiac actions of quinidine have been shown in prolongation of action potential duration, but not in the tonic and use-dependent block of the maximal velocity of action potential upstroke. To elucidate the underlying ionic mechanisms, currents through the Na, Ca and K channels were examined by using a whole-cell voltage clamp technique on isolated neonatal (< 5 day) and adult (> 3 months) rabbit cardiac myocytes under various concentrations (0.5, 1.5 and 4.5 microM) of quinidine. In neonatal and adult myocytes, quinidine caused a comparable degree of dose-dependent effects on Na currents including decrease in peak Na currents, left-shift of steady-state availability curve and slowing of the recovery from inactivation. However, the inwardly rectifier K current and the transient outward current were suppressed to a greater extent in the neonatal myocytes than in the adult (P = 0.0002 and 0.02, respectively). On the contrary, the magnitude of decrease in peak Ca currents after quinidine treatment was much smaller in the neonatal myocytes than in the adult (P = 0.01). These findings indicate that age-related ionic channel-block by quinidine is complex; and shows major differences in the Ca and K currents of cardiac myocytes. Accordingly, a differential therapeutic potential of quinidine may exist in hearts of different ages.
奎尼丁与年龄相关的心脏作用已表现为动作电位时程延长，但在动作电位上升最大速度的强直和使用依赖性阻滞方面并非如此。为了阐明潜在的离子机制，在不同浓度（0.5、1.5和4.5微摩尔）的奎尼丁作用下，采用全细胞膜片钳技术对分离的新生（<5天）和成年（>3个月）兔心肌细胞的钠、钙和钾通道电流进行了检测。在新生和成年心肌细胞中，奎尼丁对钠电流产生了相当程度的剂量依赖性效应，包括峰值钠电流降低、稳态可用性曲线左移以及失活恢复减慢。然而，内向整流钾电流和瞬时外向电流在新生心肌细胞中的抑制程度比成年心肌细胞更大（分别为P = 0.0002和0.02）。相反，奎尼丁处理后峰值钙电流的降低幅度在新生心肌细胞中比成年心肌细胞小得多（P = 0.01）。这些发现表明，奎尼丁与年龄相关的离子通道阻滞是复杂的；并且在心肌细胞的钙电流和钾电流方面存在主要差异。因此，奎尼丁在不同年龄心脏中可能存在不同的治疗潜力。
