Doltchinkova Virjinia, Mouleshkova Nevena, Vitkova Victoria
Department of Biophysics and Radiobiology, Faculty of Biology, Sofia University "St. Kliment Ohridski", 8 Dragan Tsankov Blvd., 1164 Sofia, Bulgaria.
Georgi Nadjakov Institute of Solid State Physics, Bulgarian Academy of Sciences, 72 Tsarigradsko Chaussee Blvd., 1784 Sofia, Bulgaria.
Membranes (Basel). 2021 Dec 17;11(12):987. doi: 10.3390/membranes11120987.
Morphologically and functionally identical to brain synapses, the nerve ending particles synaptosomes are biochemically derived membrane structures responsible for the transmission of neural information. Their surface and mechanical properties, measured in vitro, provide useful information about the functional activity of synapses in the brain in vivo. Glutamate and kainic acid are of particular interest because of their role in brain pathology (including causing seizure, migraine, ischemic stroke, aneurysmal subarachnoid hemorrhage, intracerebral hematoma, traumatic brain injury and stroke). The effects of the excitatory neurotransmitter L-glutamic acid and its agonist kainic acid are tested on Na, K-ATPase and Mg-ATPase activities in synaptic membranes prepared from the cerebral cortex of rat brain tissue. The surface parameters of synaptosome preparations from the cerebral cortex in the presence of L-glutamic and kainic acids are studied by microelectrophoresis for the first time. The studied neurotransmitters promote a significant increase in the electrophoretic mobility and surface electrical charge of synaptosomes at 1-4 h after isolation. The measured decrease in the bending modulus of model bimolecular membranes composed of monounsaturated lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine provides evidence for softer membranes in the presence of L-glutamate. Kainic acid does not affect membrane mechanical stability even at ten-fold higher concentrations. Both the L-glutamic and kainic acids reduce acetylcholinesterase activity and deviation from the normal functions of neurotransmission in synapses is presumed. The presented results regarding the modulation of the enzyme activity of synaptic membranes and surface properties of synaptosomes are expected by biochemical and biophysical studies to contribute to the elucidation of the molecular mechanisms of neurotransmitters/agonists' action on membranes.
神经末梢颗粒突触体在形态和功能上与脑突触相同,是负责神经信息传递的生化衍生膜结构。在体外测量其表面和机械性能,可为体内大脑突触的功能活动提供有用信息。谷氨酸和 kainic 酸因其在脑部病理学中的作用(包括引起癫痫、偏头痛、缺血性中风、动脉瘤性蛛网膜下腔出血、脑内血肿、创伤性脑损伤和中风)而备受关注。测试兴奋性神经递质 L-谷氨酸及其激动剂 kainic 酸对从大鼠脑组织大脑皮层制备的突触膜中 Na、K-ATP 酶和 Mg-ATP 酶活性的影响。首次通过微电泳研究了在 L-谷氨酸和 kainic 酸存在下大脑皮层突触体制剂的表面参数。所研究的神经递质在分离后 1-4 小时促进突触体的电泳迁移率和表面电荷显著增加。由单不饱和脂质 1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱组成的模型双分子膜弯曲模量的测量降低为 L-谷氨酸存在下膜更柔软提供了证据。即使在浓度高出十倍的情况下,kainic 酸也不影响膜的机械稳定性。L-谷氨酸和 kainic 酸均降低乙酰胆碱酯酶活性,并推测突触中神经传递正常功能出现偏差。关于突触膜酶活性调节和突触体表面性质的研究结果,预计将通过生化和生物物理研究,有助于阐明神经递质/激动剂对膜作用的分子机制。