DeRiemer S A, Schweitzer B, Kaczmarek L K
Brain Res. 1985 Aug 5;340(1):175-80. doi: 10.1016/0006-8993(85)90790-5.
Experiments with isolated bag cell neurons of Aplysia have produced evidence that changes in neuronal excitability may be brought about by the activation of calcium dependent enzymes such as calcium-dependent protein kinases. We have now examined the effects of agents which have been shown to inhibit several calcium-dependent enzymes on the properties of bag cell neurons in situ. In response to brief electrical stimulation the bag cell neurons of Aplysia generate an afterdischarge during which they release neuroactive peptides. We have found that the ability of stimulation to trigger an afterdischarge in the bag cell neurons is inhibited by trifluoperazine (TFP, 50-100 microM), N-(6-aminohexyl)-5-chloro-1-napthalenesulphonamide (W7) (25-50 microM) and calmidazolium (40-100 microM), each of which has previously been shown to inhibit calmodulin-dependent enzymes and the calcium-phospholipid-dependent protein kinase in the bag cell neurons. Further analysis of the effects of TFP showed that this inhibition occurs at concentrations which do not inhibit synaptic transmission or the endogenous bursting of another neurosecretory neuron, R15. Secretion of neuroactive peptides from the bag cell neurons was measured both electrophysiologically and biochemically. No attenuation of secretion could be observed at concentrations of TFP below those which inhibited the initiation of afterdischarge. Our results indicate that these agents inhibit secretion from these neurons primarily by inhibiting the onset of the afterdischarge and are consistent with the hypothesis that a calcium-dependent enzyme plays a role in triggering the stimulus-induced transformation in the electrical properties of these neurons.
对海兔分离的袋状细胞神经元进行的实验已得出证据，表明神经元兴奋性的变化可能是由钙依赖性酶（如钙依赖性蛋白激酶）的激活所引起的。我们现在研究了已被证明能抑制几种钙依赖性酶的药物对原位袋状细胞神经元特性的影响。响应短暂的电刺激，海兔的袋状细胞神经元会产生一个后放电过程，在此期间它们会释放神经活性肽。我们发现，三氟拉嗪（TFP，50 - 100微摩尔）、N -（6 - 氨基己基）- 5 - 氯 - 1 - 萘磺酰胺（W7）（25 - 50微摩尔）和平静咪（40 - 100微摩尔）会抑制刺激在袋状细胞神经元中触发后放电的能力，此前已证明每种药物都能抑制袋状细胞神经元中的钙调蛋白依赖性酶和钙 - 磷脂依赖性蛋白激酶。对TFP作用的进一步分析表明，这种抑制作用发生在不抑制突触传递或另一种神经分泌神经元R15的内源性爆发的浓度下。通过电生理学和生物化学方法测量了袋状细胞神经元中神经活性肽的分泌。在低于抑制后放电起始浓度的TFP浓度下，未观察到分泌的减弱。我们的结果表明，这些药物主要通过抑制后放电的起始来抑制这些神经元的分泌，这与钙依赖性酶在触发这些神经元电特性的刺激诱导转变中起作用的假设是一致的。
