THE MOLECULAR BASIS OF MEMBRANE EXCITABILITY

被归因于钠通道门运动的不对称电流 在不同的组织中测量。在青蛙骨骼肌不对称电流中， 与从巨型轴突记录到的类似，已经在纤维中测量到 钠电导限值范围宽。不对称电荷不是 与极限钠电导成正比。保持在-150 mV将使 步进到0 mV时移动的电荷量，与保持在-90 mV时相比。 这两个观测结果表明，一些快速不对称电流测量在 蛙肌不是功能性钠门控电流。两种类型的实验将 以努力区分功能门控和非功能门控 电流。首先，在持有时，电荷的运动动力学 -150 mV的电势将与可移动的电荷的动力学进行比较 保持电位为-90 mV。第二，将乌头碱用于修饰 钠通道的动力学。通过确定门控电荷的比例 改进的动力学应该可以分离功能门控电荷 来自其他不对称电荷。 乌头碱可降低钠电导峰值。单通道电导将为 测量以确定这种抑郁是否是由于 通道或降低的单通道电导。TTX的可能性 对乌头碱修饰钠通道的保护也将是 调查过了。 这种巨大的变异性限制了在青蛙抽动肌肉中测量的钠电导 这很可能是青蛙物种、季节或地理变异的结果。 将努力开发一种哺乳动物肌肉门控电流制剂 没有这些缺点。

Asymmetric currents attributed to the movement of the Na channel gates have been measured in various tissues. In frog skeletal muscle asymmetric currents, similar to those recorded from giant axons, has been measured in fibers with a wide range of limitation sodium conductances. Asymmetric charge is not proportional to limiting sodium conductance. Holding at -150 mV doubles the amount of charge moved when stepping to 0 mV, compared to holding at -90 mV. These two observations imply that some of the fast asymmetric current measure in frog muscle is not functional Na gating current. Two kinds of experiments will be performed in an effort to distinguish functional from non-functional gating current. First, the kinetics of the charge that becomes mobile at a holding potential of -150 mV will be compared with the kinetics of charge that is mobile at a holding potential of -90 mV. Second, aconitine will be used to modify kinetics of Na channels. By determining the portion of gating charge with modified kinetics it should be possible to separate functional gating charge from other asymmetric charge. Aconitine depresses peak sodium conductance. Single channel conductance will be measured in order to determine whether this depression is due to loss of channels or to decreased single channel conductance. The possibility that TTX protects against aconitine modification of sodium channels will also be investigated. The large variability is limiting Na conductances measured in frog twitch muscle is likely a consequence of species, seasonal or geographic variability in frogs. Efforts will be made to develop a mammalian muscle gating current preparation without these disadvantages.