Nobile M, Magnelli V, Lagostena L, Mochca-Morales J, Possani L D, Prestipino G
Istituto di Cibernetica e Biofisica, CNR, Genova, Italy.
J Membr Biol. 1994 Apr;139(1):49-55. doi: 10.1007/BF00232674.
Helothermine, a recently isolated toxin from the venom of the Mexican beaded lizard Heloderma horridum horridum was tested on K+ currents of newborn rat cerebellar granule cells. In whole-cell voltage-clamp experiments, cerebellar granule neurons exhibited at least two different K+ current components: a first transient component which is similar to an IA-type current, is characterized by fast activating and inactivating kinetics and blocked by 4-aminopyridine; a second component which is characterized by noninactivating kinetics, is blocked by tetraetylammonium ions and resembles the classical delayed-rectifier current. When added to the standard external solution at concentrations ranging between 0.1 and 2 microM, helothermine reduced the pharmacologically isolated IA-type current component in a voltage- and dose-dependent way, with a half-maximal inhibitory concentration (IC50) of 0.52 microM. A comparison between control and helothermine-modified peak transient currents shows a slowdown of activation and inactivation kinetics. The delayed-rectifier component inhibition was concentration dependent (IC50 = 0.86 microM) but not voltage dependent. No frequency- or use-dependent block was observed on both K+ current types. Perfusing the cells with control solution resulted in quite a complete current recovery. We conclude that helothermine acts with different affinities on two types of K+ current present in central nervous system neurons.
从墨西哥珠毒蜥（Heloderma horridum horridum）毒液中最近分离出的毒素——Helothermine，被用于测试新生大鼠小脑颗粒细胞的钾离子电流。在全细胞膜片钳实验中，小脑颗粒神经元表现出至少两种不同的钾离子电流成分：第一种是瞬态成分，类似于IA型电流，其特征是激活和失活动力学快速，并被4-氨基吡啶阻断；第二种成分的特征是非失活动力学，被四乙铵离子阻断，类似于经典的延迟整流电流。当以0.1至2微摩尔的浓度添加到标准外部溶液中时，Helothermine以电压和剂量依赖性方式降低了药理学分离出的IA型电流成分，半数最大抑制浓度（IC50）为0.52微摩尔。对照和Helothermine修饰的峰值瞬态电流之间的比较显示激活和失活动力学减慢。延迟整流成分的抑制是浓度依赖性的（IC50 = 0.86微摩尔），但不是电压依赖性的。在两种钾离子电流类型上均未观察到频率或使用依赖性阻断。用对照溶液灌注细胞可使电流相当完全地恢复。我们得出结论，Helothermine对中枢神经系统神经元中存在的两种类型的钾离子电流具有不同的亲和力。
