The chemotherapeutic oxaliplatin alters voltage-gated Na+ channel kinetics on rat sensory neurons
The chemotherapeutic oxaliplatin alters voltage-gated Na+ channel kinetics on rat sensory neurons
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DOI：
10.1016/s0014-2999(00)00667-1
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发表时间：
2000-10-06
影响因子：
5
通讯作者：
Lersch, C
中科院分区：
文献类型：
--
作者：
Adelsberger, H;Quasthoff, S;Lersch, C
化疗药物奥沙利铂引起感觉运动神经病，主要表现为过敏性症状。用大鼠感觉神经标本、背根神经节和海马神经元研究了这种高兴奋性的机制。奥沙利铂可使复合动作电位的波幅和时程增加。延长外周神经不应期，提示与电压门控性Na+通道相互作用。背根神经节神经元应用奥沙利铂后，Na+电流增加，最大幅度被阻断，电压-反应关系向更负的膜电位移动。在18个测试细胞中，有13个细胞可以检测到这种影响。这一观察结果，再加上对海马神经元Na+电流没有任何影响，表明奥沙利铂的相互作用仅限于一个或多个通道亚型。钠通道阻滞剂卡马西平可拮抗奥沙利铂的作用，卡马西平可用于减少奥沙利铂治疗的副作用。(C)2000 Elsevier Science B.V.保留所有权利。
The chemotherapeutic oxaliplatin causes a sensory-motor neuropathy with predominantly hyperpathic symptoms. The mechanism underlying this hyperexcitability was investigated using rat sensory nerve preparations, dorsal root ganglia and hippocampal neurons. Oxaliplatin resulted in an increase of the amplitude and duration of compound action potentials. It lengthened the refractory period of peripheral nerves suggesting an interaction with voltage-gated Na+ channels. Application of oxaliplatin to dorsal root ganglion neurons resulted in an increase of the Na+ current, a block of the maximal amplitude and a shift of the voltage-response relationship towards more negative membrane potentials. The effect was detectable on 13 of 18 tested cells. This observation, together with the absence of any effect on Na+ currents of hippocampal neurons, suggests that the interaction of oxaliplatin is restricted to one or more channel subtypes. The effect of oxaliplatin could be antagonised by the Na+ channel blocker carbamazepine which could be used to reduce side effects of oxaliplatin therapy in patients. (C) 2000 Elsevier Science B.V. All rights reserved.