Furue T, Yakehiro M, Yamaoka K, Sumii K, Seyama I
Department of Physiology, Hiroshima University School of Medicine Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan.
Pflugers Arch. 1998 Oct;436(5):631-8. doi: 10.1007/s004240050682.
Inactivation of the fast Na+ current of heart muscle occurs in two kinetically distinct phases: a fast process operating on a millisecond time scale and a considerably slower process, the kinetic properties of which have not been explored fully. In this study, we analysed the slow inactivation process in isolated frog ventricular myocytes using the whole-cell variation of the patch-clamp method. Slow inactivation of the Na+ current followed a double-exponential time course, corresponding to slow and ultraslow components of Na+ channel inactivation. The individual time constants were 2-7 s (slow component) and 40-560 s (ultraslow component). Recovery from these slow inactivation processes also followed a double-exponential time course, but was characterized by significantly briefer time constants than those for the inactivation process. The relationship between transmembrane potential and steady-state slow or ultraslow inactivation was well described by the Boltzmann equation. The membrane potential at which half the Na+ channels are inactivated (V1/2) and the slope factor were estimated to be -48.1 and 13.6 mV, respectively, for the slow component alone. Under conditions in which the slow and ultraslow inactivation components were both present, these parameters were -53.1 and 8.7 mV respectively. When the fast and the two slow inactivation processes occurred concomitantly, the resultant steady-state inactivation curves were shifted to more negative potentials and the slope factor was decreased. Treatment with 1 mM Cd2+ externally did not affect the time course of slow inactivation, but produced a 3-7 mV depolarizing shift in its steady-state voltage dependency by virtue of cadmium's known effect on the cell surface potential. This study has thus identified two components of slow Na+ inactivation in heart muscle, operating on a time scale of seconds (slow inactivation) and minutes (ultraslow inactivation).
一个在毫秒时间尺度上起作用的快速过程和一个显著较慢的过程，其动力学特性尚未得到充分研究。在本研究中，我们使用膜片钳方法的全细胞变体分析了分离的青蛙心室肌细胞中的慢失活过程。钠电流的慢失活遵循双指数时间进程，对应于钠通道失活的慢成分和超慢成分。各个时间常数分别为2 - 7秒（慢成分）和40 - 560秒（超慢成分）。从这些慢失活过程中的恢复也遵循双指数时间进程，但其特征是时间常数比失活过程的显著更短。跨膜电位与稳态慢或超慢失活之间的关系可以用玻尔兹曼方程很好地描述。仅对于慢成分，一半钠通道失活时的膜电位（V1/2）和斜率因子估计分别为 - 48.1和13.6 mV。在慢失活和超慢失活成分都存在的条件下，这些参数分别为 - 53.1和8.7 mV。当快速和两个慢失活过程同时发生时，所得的稳态失活曲线向更负的电位移动，并且斜率因子减小。外部用1 mM Cd2+处理不影响慢失活的时间进程，但由于镉对细胞表面电位的已知作用，使其稳态电压依赖性产生3 - 7 mV的去极化偏移。因此，本研究确定了心肌中慢钠失活的两个成分，分别在秒（慢失活）和分钟（超慢失活）的时间尺度上起作用。
