Rentas A L, Rosa R, Rodríguez A D, De Motta G E
Department of Biology, University of Puerto Rico, San Juan 00901.
Toxicon. 1995 Apr;33(4):491-7. doi: 10.1016/0041-0101(94)00164-4.
Dibromosceptrin and clathrodin are alkaloid compounds purified from tropical marine sponges of the genus Agelas. Experiments done using the whole cell configuration of the patch clamp technique revealed that these compounds have neurotoxic activity. Both compounds decreased by 27-40% the average maximum amplitudes of pharmacologically isolated inward sodium currents in cells isolated from chick embryo sympathetic ganglia. Current-voltage data, fitted using Boltzmann's equation, did not show any effect of these agents on the voltage dependence of current activation. However, the voltage dependence of current inactivation was shifted toward more negative potentials by dibromosceptrin, changing by an average of 20 mV the voltage for 50% inactivation. In contrast, clathrodin shifted this voltage dependence of inactivation toward more positive potentials and changed the voltage for 50% inactivation by 14 mV. Time for current reactivation was not altered by clathrodin but was slightly prolonged by dibromosceptrin. Similarly, dibromosceptrin was more effective than clathrodin in delaying the time course of current decay. Thus, these two alkaloids appear to be new sodium channel neurotoxins acting through different mechanisms, dibromosceptrin modifying the channel inactivation characteristics and clathrodin probably influencing channel ionic conductance.
二溴海鞘素和网格菌素是从艾氏海绵属热带海洋海绵中纯化得到的生物碱化合物。使用膜片钳技术的全细胞配置进行的实验表明，这些化合物具有神经毒性活性。这两种化合物均使从鸡胚交感神经节分离的细胞中经药理学分离的内向钠电流的平均最大幅度降低了27 - 40%。使用玻尔兹曼方程拟合的电流 - 电压数据未显示这些药物对电流激活的电压依赖性有任何影响。然而，二溴海鞘素使电流失活的电压依赖性向更负的电位移动，使50%失活的电压平均变化了20 mV。相比之下，网格菌素使这种失活的电压依赖性向更正的电位移动，并使50%失活的电压变化了14 mV。电流再激活时间未被网格菌素改变，但被二溴海鞘素略微延长。同样，在延迟电流衰减的时间进程方面，二溴海鞘素比网格菌素更有效。因此，这两种生物碱似乎是通过不同机制起作用的新型钠通道神经毒素，二溴海鞘素改变通道失活特性，而网格菌素可能影响通道离子电导。
