Nistri A
Department of Pharmacology, Queen Mary and Westfield College, London, U.K.
Ann Ital Med Int. 1990 Jul-Sep;5(3 Pt 2):245-8.
Thyrotropin releasing hormone (TRH), an endogenous tripeptide of the spinal cord, is being used in clinical trials for the treatment of neurological disorders involving the spinal function. Experiments have been carried out on rat lumbar motoneurons identified by their action potentials evoked by antidromic ventral root stimulation. Glass microelectrodes containing a concentrated KCl solution were used for intracellular electrophysiological findings while the specimen was continuously perfused with oxygenated saline solution. Previous experiments conducted in our laboratory had shown that TRH (50 mumol) has an intense depolarizing activity on frog motoneurons and that it is capable of considerably increasing excitatory postsynaptic potentials. In an ongoing trial in rat neurons we have observed how TRH produces slowly developing but persisting motoneuron depolarization characterized by steady action potential discharges. This phenomenon is different from the much more rapid and shorter effect of glutamate which is thought to be the excitatory neurotransmitter of these neurons. The capacity of TRH to generate a series of action potentials without any apparent "fatigue" is an interesting and unusual property. In order to explain this property we pharmacologically isolated the neurons by means of tetrodotoxin treatment and recorded their ionic conductance. While TRH was acting the conductance decreased considerably, indicating that synaptic signals are amplified in this new condition of the postsynaptic membrane. Voltage clamp studies have suggested that this decrease in conductance occurs within a range of relatively negative membrane potentials and probably consists in the blocking of voltage-dependent, tendentially repolarizing ion channels (perhaps potassium).(ABSTRACT TRUNCATED AT 250 WORDS)
促甲状腺激素释放激素（TRH）是脊髓中的一种内源性三肽，目前正用于治疗涉及脊髓功能的神经疾病的临床试验。我们对通过逆向腹根刺激诱发动作电位来识别的大鼠腰段运动神经元进行了实验。含有高浓度氯化钾溶液的玻璃微电极用于细胞内电生理研究，同时标本持续灌注含氧生理盐水溶液。我们实验室之前进行的实验表明，TRH（50微摩尔）对青蛙运动神经元有强烈的去极化活性，并且能够显著增加兴奋性突触后电位。在一项针对大鼠神经元的正在进行的试验中，我们观察到TRH如何产生缓慢发展但持续存在的运动神经元去极化，其特征是稳定的动作电位发放。这种现象与谷氨酸的作用明显不同，谷氨酸的作用更快、更短暂，被认为是这些神经元的兴奋性神经递质。TRH能够在没有任何明显“疲劳”的情况下产生一系列动作电位，这是一个有趣且不寻常的特性。为了解释这一特性，我们通过河豚毒素处理从药理学上分离出神经元，并记录它们的离子电导。当TRH起作用时，电导显著降低，这表明在突触后膜的这种新状态下突触信号被放大。电压钳研究表明，这种电导降低发生在相对负的膜电位范围内，可能是由于电压依赖性、倾向于复极化的离子通道（可能是钾通道）被阻断。（摘要截选至250词）
