Smejtek P, Riker W K, Wright C, Bennett M J
Department of Physics and Environmental Sciences, Portland State University, OR 97207-0751.
Biochim Biophys Acta. 1990 Nov 16;1029(2):259-66. doi: 10.1016/0005-2736(90)90162-h.
Aminopyridines belong to the class of compounds which facilitate synaptic transmission at low calcium concentration, an effect associated with the block of K+ channels, enhanced entry of calcium into presynaptic terminals and greater release of transmitter. We have measured the zeta-potential of phosphatidylserine vesicles in the presence of aminopyridines and some related compounds in order to relate the strength of association of the aminopyridines with their biological effectiveness. The dependence of zeta-potential on the concentration of aminopyridines was analyzed in terms of the Langmuir-Stern-Grahame adsorption model. The rank order of the association constants (in M-1) obtained in the study was as follows: 3,4-diaminopyridine (6.5), 4,5-diaminopyrimidine (3.8), 4-aminopyridine (2.6), 3-aminopyridine (1.8), 2-aminopyridine (1.6), 4-dimethylaminopyridine (0.5), 4-aminopyridine methiodide (0.2), and, as control, calcium (12.1). The comparison of association constants with published results of the electric potential maps obtained by the CNDO/2 method suggests that binding to phosphatidylserine membrane increases with the density of excess charge on the protonated aminopyridine ring. We find that the sequence of potencies of aminopyridines in blocking K+ channels, in releasing transmitter, and in the shifts of calcium concentration dependence of synaptic transmission are about the same as the sequence of association constants with the phosphatidylserine membrane. Assuming that the binding domain for aminopyridines in the presynaptic terminal has similar adsorption properties as the phosphatidylserine membrane, we estimate the electric potential difference between the domain and the external solution to be between -300 and -340 mV.
氨基吡啶属于一类化合物，这类化合物在低钙浓度下可促进突触传递，该效应与钾离子通道的阻断、钙离子进入突触前终末的增加以及递质释放的增多有关。我们测定了在氨基吡啶及一些相关化合物存在的情况下磷脂酰丝氨酸囊泡的ζ电位，以便将氨基吡啶的结合强度与其生物学效应联系起来。根据朗缪尔 - 斯特恩 - 格雷厄姆吸附模型分析了ζ电位对氨基吡啶浓度的依赖性。本研究中获得的结合常数（单位为M⁻¹）的排序如下：3,4 - 二氨基吡啶（6.5）、4,5 - 二氨基嘧啶（3.8）、4 - 氨基吡啶（2.6）、3 - 氨基吡啶（1.8）、2 - 氨基吡啶（1.6）、4 - 二甲氨基吡啶（0.5）、4 - 氨基吡啶甲碘化物（0.2），作为对照的钙（12.1）。将结合常数与通过CNDO/2方法获得的电势图的已发表结果进行比较表明，与磷脂酰丝氨酸膜的结合随着质子化氨基吡啶环上过量电荷的密度增加而增强。我们发现氨基吡啶在阻断钾离子通道、释放递质以及突触传递的钙浓度依赖性变化方面的效力顺序与它们与磷脂酰丝氨酸膜的结合常数顺序大致相同。假设突触前终末中氨基吡啶的结合域具有与磷脂酰丝氨酸膜相似的吸附特性，我们估计该域与外部溶液之间的电势差在 - 300至 - 340 mV之间。
