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)