Halliwell J V, Othman I B, Pelchen-Matthews A, Dolly J O
Proc Natl Acad Sci U S A. 1986 Jan;83(2):493-7. doi: 10.1073/pnas.83.2.493.
Dendrotoxin, a small single-chain protein from the venom of Dendroaspis angusticeps, is highly toxic following intracerebroventricular injection into rats. Voltage-clamp analysis of CA1 neurons in hippocampal slices, treated with tetrodotoxin, revealed that nanomolar concentrations of dendrotoxin reduce selectively a transient, voltage-dependent K conductance. Epileptiform activity known to be induced by dendrotoxin can be attributed to such an action. Membrane currents not affected directly by the toxin include (i) Ca-activated K conductance; (ii) noninactivating voltage-dependent K conductance; (iii) inactivating and noninactivating Ca conductances; (iv) persistent inward (anomalous) rectifier current. Persistence of the effects of the toxin when Cd was included to suppress spontaneous transmitter release indicates a direct action on the neuronal membrane. Using biologically active, 125I-labeled dendrotoxin, protein acceptor sites of high affinity were detected on cerebrocortical synaptosomal membranes and sections of rat brain. In hippocampus, toxin binding was shown autoradiographically to reside in synapse-rich and white matter regions, with lower levels in cell body layers. This acceptor is implicated in the action of toxin because its affinities for dendrotoxin congeners are proportional to their central neurotoxicities and potencies in reducing the transient, voltage-dependent K conductance.
树眼镜蛇毒素是一种来自绿曼巴蛇毒液的小分子单链蛋白质，对大鼠进行脑室内注射后具有高度毒性。对用河豚毒素处理过的海马切片中的CA1神经元进行电压钳分析表明，纳摩尔浓度的树眼镜蛇毒素可选择性地降低一种短暂的、电压依赖性钾电导。已知由树眼镜蛇毒素诱导的癫痫样活动可归因于这种作用。不受毒素直接影响的膜电流包括：（i）钙激活钾电导；（ii）非失活电压依赖性钾电导；（iii）失活和非失活钙电导；（iv）持续性内向（异常）整流电流。当加入镉以抑制自发递质释放时毒素作用仍然存在，这表明毒素对神经元膜有直接作用。使用具有生物活性的125I标记树眼镜蛇毒素，在大鼠脑皮质突触体膜和脑切片上检测到了高亲和力的蛋白质受体位点。在海马体中，放射自显影显示毒素结合存在于富含突触的区域和白质区域，在细胞体层中的水平较低。这种受体与毒素的作用有关，因为它对树眼镜蛇毒素同系物的亲和力与其中枢神经毒性以及降低短暂电压依赖性钾电导的效力成正比。
