Pivovarov Arkady S, Murzina Galina B, Makhnovsky Denis A, Tret'yakova Mariya S, Vasil'yeva Natalya A
Department of Higher Nervous Activity, Biological Faculty, Lomonosov State University, Moscow, 119991, Russia,
Invert Neurosci. 2013 Dec;13(2):135-50. doi: 10.1007/s10158-013-0155-z. Epub 2013 Apr 17.
We investigated the role of the mobility of acetylcholine receptors in the depression of an acetylcholine-induced inward current (ACh-current) of Helix lucorum (a land snail) command neurons of defensive behavior in a cellular analog of habituation. The inhibitors of endocytosis and exocytosis, actin microfilaments and cytoskeleton microtubules, serine/threonine protein kinases (PKA, PKG, calcium calmodulin-dependent PK II, p38 mitogen-activated PK), tyrosine kinases (including Src-family kinases), serine/threonine phosphatases (PP1, PP2A, PP2B, PPM1D), and tyrosine protein phosphatases altered the depression of the ACh-current. A comparison of experimentally calculated curves of the ACh-current of these neurons and those obtained by mathematical modeling revealed the following: (a) ACh-current depression is caused by the reduction in the number of membranous ACh-receptors, which results from the shift in the balance of multidirectional transport processes of receptors toward the predominance of ACh-receptor internalization over their recycling; (b) depression of ACh-current depends on the activity of serine/threonine and tyrosine protein kinases and protein phosphatases, whose one of the main targets is the neuron transport system-actin microfilaments and microtubules of cytoskeleton, as well as motor proteins.
我们在一种习惯化的细胞模型中,研究了乙酰胆碱受体的移动性在抑制福寿螺(一种陆地蜗牛)防御行为的指令神经元的乙酰胆碱诱导内向电流(ACh电流)中的作用。内吞作用和外排作用、肌动蛋白微丝和细胞骨架微管、丝氨酸/苏氨酸蛋白激酶(蛋白激酶A、蛋白激酶G、钙调蛋白依赖性蛋白激酶II、p38丝裂原活化蛋白激酶)、酪氨酸激酶(包括Src家族激酶)、丝氨酸/苏氨酸磷酸酶(蛋白磷酸酶1、蛋白磷酸酶2A、蛋白磷酸酶2B、蛋白磷酸酶M1D)以及酪氨酸蛋白磷酸酶的抑制剂,均改变了ACh电流的抑制作用。对这些神经元的ACh电流的实验计算曲线与通过数学建模获得的曲线进行比较后发现:(a)ACh电流的抑制是由于膜性ACh受体数量减少所致,这是由受体多向运输过程的平衡向ACh受体内化超过其再循环的优势方向转变所导致的;(b)ACh电流的抑制取决于丝氨酸/苏氨酸和酪氨酸蛋白激酶以及蛋白磷酸酶的活性,其主要靶点之一是神经元运输系统——细胞骨架的肌动蛋白微丝和微管以及运动蛋白。