Nelson J C, Wyman R J
Department of Biology, Yale University, New Haven, Connecticut 06511.
J Neurobiol. 1990 Apr;21(3):453-69. doi: 10.1002/neu.480210307.
We have used the identified cells of the Drosophila Giant Fiber System (GFS) to study the defects induced by the temperature-sensitive paralytic mutations no action potential (nap) and paralytic (para). These mutations paralyze at elevated temperatures, reported as due to a block of action potential propagation. We found, however, that the cells of the GFS still were able to respond to stimuli at 7-10 degrees C above the temperature causing mutant paralysis. Stimulus threshold and conduction time both decrease with increasing temperature in the mutants in a manner indistinguishable from wild-type. Since action potentials can propagate efficiently in the mutants at elevated temperatures, we looked for other neural defects that might be involved in producing paralysis. We did find reduced neuronal function at sites such as electrical synapses and axonal branch points where current may be limiting. These sites had weakened following frequency, occasional failures, and increased conduction times. We believe the non-temperature-dependent defects in nap and para uncover the normally temperature-sensitive traits latent within all neurons. Increasing temperature increases the rates of channel activation and inactivation. At higher temperatures, Na+ inactivation and K+ activation encroach upon the Na(+)-activation time, reducing inward sodium current. In addition to this normal temperature-dependent effect, the mutations decrease the number of sodium channels in neurons in a non-temperature-dependent manner. These two reductions in sodium current combine to prevent spiking threshold from being reached at current limited sites. The temperature at which a sufficient number of these sites block should be the temperature of paralysis.
我们利用果蝇巨纤维系统（GFS）中已识别的细胞，来研究温度敏感型麻痹突变“无动作电位”（nap）和“麻痹”（para）所诱发的缺陷。这些突变在温度升高时会导致麻痹，据报道这是由于动作电位传播受阻所致。然而，我们发现，在比导致突变体麻痹的温度高7 - 10摄氏度时，GFS的细胞仍然能够对刺激做出反应。在突变体中，刺激阈值和传导时间均随温度升高而降低，其方式与野生型无法区分。由于在温度升高时动作电位能够在突变体中有效传播，我们便寻找其他可能与麻痹产生有关的神经缺陷。我们确实在诸如电突触和轴突分支点等电流可能受限的部位发现了神经元功能的降低。这些部位的跟随频率减弱、偶尔出现传导失败且传导时间增加。我们认为nap和para中与温度无关的缺陷揭示了所有神经元中潜在的通常对温度敏感的特性。温度升高会增加通道激活和失活的速率。在较高温度下，Na⁺失活和K⁺激活会侵占Na⁺激活时间，减少内向钠电流。除了这种正常的温度依赖性效应外，这些突变还以与温度无关的方式减少神经元中钠通道的数量。这两种钠电流的减少共同作用，使得在电流受限部位无法达到激发阈值。这些部位出现足够数量阻滞的温度应该就是麻痹发生的温度。
