THE MOLECULAR BASIS OF MEMBRANE EXCITABILITY

归因于钠通道门运动的不对称电流已经被发现 在各种组织中测量。 在青蛙骨骼肌不对称电流中， 类似于从巨大轴突记录的那些，已经在纤维中测量到， 宽范围的限制钠电导。 不对称电荷不是 与极限钠电导率成正比。 保持在-150 mV时， 与保持在-90 mV时相比，步进到0 mV时移动的电荷量。 这两个观察结果意味着，一些快速不对称电流的措施， 蛙肌没有功能性钠门控电流。 两种实验将 以区分功能性和非功能性门控 电流 首先，电荷在保持时变为移动的的动力学 将-150 mV的电势与移动的电荷动力学进行比较 保持电位为-90 mV。 二是将乌头碱用于修饰 Na通道动力学 通过确定门控电荷的部分， 改进的动力学，应该可以分离功能性门控电荷， 其他不对称电荷。 乌司他丁降低峰值钠电导。 单通道电导将是 测量，以确定这种抑郁症是否是由于损失的 通道或降低的单通道电导。 TTX可能 还可防止钠通道的乌头碱修饰， 研究了 大的可变性限制了在青蛙抽搐肌肉中测量的Na电导 很可能是青蛙的物种、季节或地理变异的结果。 将努力开发哺乳动物肌门控电流制剂 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.