Wu M H, Su M J, Lue H C
Department of Pediatrics, National Taiwan University Hospital, College of Medicine, Taipei, R.O.C.
J Formos Med Assoc. 1993 Feb;92(2):103-9.
Using the whole-cell voltage clamp method, sodium (Na) channel properties and their responses to lidocaine were studied in ventricular myocytes isolated from neonatal (N, < 3 days), infant (I, 10-17 days) and mature (M, > 3 months) rabbits. Developmental changes in the Na channels were characterized by a progressive right-shift in the inactivation curves and a faster recovery from inactivation. Lidocaine (10 microM) effectively reduced the peak Na currents in M myocytes, but had little affect on the current-voltage curve in N myocytes. The steady-state h inactivation curve shifted toward the left (ie, more negative potentials) after lidocaine, and the extent of the left-shift increased with maturation. Similarly, the magnitude of prolongation in Na channel recovery from inactivation by lidocaine increased with age. However, lidocaine at a higher concentration (30 microM) in N myocytes effectively blocked the Na channels, and the degree of suppression was comparable to that in M myocytes with 10 microM lidocaine. These data suggest that the Na channels of N myocytes per se are less sensitive to lidocaine. The results of this study indicate that the extent of Na channel inactivation becomes smaller during postnatal maturation. However, the Na channel of immature myocytes is less sensitive to the widely used Na channel blocker, lidocaine, which preferentially binds to the inactive state of the Na channel.
采用全细胞膜片钳技术，研究了从新生（N，<3天）、幼龄（I，10 - 17天）和成年（M，>3个月）兔分离的心室肌细胞中钠（Na）通道特性及其对利多卡因的反应。钠通道的发育变化表现为失活曲线逐渐右移以及失活后恢复更快。利多卡因（10μM）有效降低了成年心肌细胞的钠电流峰值，但对新生心肌细胞的电流 - 电压曲线影响较小。利多卡因作用后，稳态h失活曲线向左移动（即更负的电位），且左移程度随成熟度增加。同样，利多卡因使钠通道从失活状态恢复的延长幅度随年龄增加。然而，新生心肌细胞中较高浓度（30μM）的利多卡因可有效阻断钠通道，抑制程度与成年心肌细胞中10μM利多卡因相当。这些数据表明新生心肌细胞的钠通道本身对利多卡因不太敏感。本研究结果表明，出生后成熟过程中钠通道失活程度变小。然而，未成熟心肌细胞的钠通道对广泛使用的钠通道阻滞剂利多卡因不太敏感，利多卡因优先结合钠通道的失活状态。
