Ryzhkina Irina, Murtazina Lyaisan, Gainutdinov Khalil, Konovalov Alexander
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russia.
Zavoisky Physical-Technical Institute, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russia.
Front Chem. 2021 Mar 16;9:623860. doi: 10.3389/fchem.2021.623860. eCollection 2021.
A variety of physicochemical methods were used to examine the self-organization, physicochemical, UV absorption, and fluorescent properties of diluted aqueous solutions (calculated concentrations from 1·10 to 1·10 M) of the membrane voltage-dependent potassium channels blocker 4-aminopyridine (4-AP). Using the dynamic light scattering method, it was shown that 4-AP solutions at concentrations in the range of 1·10-1·10 M are dispersed systems in which domains and nanoassociates of hundreds of nm in size are formed upon dilution. An interrelation between the non-monotonic concentration dependencies of the size of the dispersed phase, the fluorescence intensity ( 225 nm, 340 nm), specific electrical conductivity, and pH has been established. This allows us to predict the bioeffects of the 4-AP systems at low concentrations. The impact of these diluted aqueous systems on the electrical characteristics of identified neurons of snails was studied. Incubation of neurons in the 4-AP systems for which the formation of domains and nanoassociates had been established lead to a nonmonotonic decrease of the resting potential by 7-13%. An analysis of the obtained results and published data allows for a conclusion that a consistent change in the nature and parameters of the dispersed phase, as well as the pH of the medium, apparently determines the nonmonotonic nature of the effect of the 4-AP systems in a 1·10-1·10 M concentration range on the resting membrane potential of neurons. It was found that the pre-incubation of neurons in the 4-AP system with a concentration of 1·10 M led to a 17.0% synergistic decrease in the membrane potential after a subsequent treatment with 1·10 M 4-AP solution. This finding demonstrates a significant modifying effect of self-organized dispersed systems of 4-AP in low concentrations on the neurons' sensitivity to 4-AP.
采用多种物理化学方法研究了膜电压依赖性钾通道阻滞剂4-氨基吡啶（4-AP）稀释水溶液（计算浓度为1·10至1·10 M）的自组装、物理化学、紫外吸收和荧光性质。使用动态光散射法表明，浓度在1·10-1·10 M范围内的4-AP溶液是分散体系，稀释时会形成尺寸达数百纳米的域和纳米聚集体。已确定分散相尺寸、荧光强度（225 nm、340 nm）、比电导率和pH的非单调浓度依赖性之间的相互关系。这使我们能够预测低浓度下4-AP体系的生物效应。研究了这些稀释水溶液体系对蜗牛已鉴定神经元电特性的影响。将神经元培养在已确定形成域和纳米聚集体的4-AP体系中，导致静息电位非单调下降7-13%。对所得结果和已发表数据的分析得出结论，分散相的性质和参数以及介质的pH值的一致变化，显然决定了4-AP体系在1·10-1·10 M浓度范围内对神经元静息膜电位影响的非单调性质。发现将神经元在浓度为1·10 M的4-AP体系中预孵育，随后用1·10 M 4-AP溶液处理后，膜电位会协同下降17.0%。这一发现表明低浓度下4-AP的自组装分散体系对神经元对4-AP的敏感性具有显著的调节作用。
