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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 −20  to 1·10 −2  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 −20 –1·10 −6  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 ( λ   ex  225 nm,  λ   em  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  Helix lucorum  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 −20 –1·10 −6  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 −12  M led to a 17.0% synergistic decrease in the membrane potential after a subsequent treatment with 1·10 −2  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.

frontiers in chemistry

Diluted Aqueous Dispersed Systems of 4-Aminopyridine: The Relationship of Self-Organization, Physicochemical Properties, and Influence on the Electrical Characteristics of Neurons