Evidence for taurine as an inhibitory neurotransmitter in cerebellar stellate interneurons: selective antagonism by TAG (6-aminomethyl-3-methyl-4H,1,2,4-benzothiadiazine-1,1-dioxide)

Abstract

Using a novel amino acid antagonist, TAG (6-aminomethyl-3-methyl-4H,1,2,4-benzothiadiazine-1,1-dioxide), intradendritic electrophysiological investigations were carried out to obtain evidence for taurine as a neurotransmitter in the cerebellum. The hyperpolarizing action of taurine on Purkinje cell dendrites in guinea pig cerebellar slices was selectively antagonized by TAG (200 microM), while the actions of GABA, glycine and beta-alanine were virtually unaffected. TAG shifted the log dose-response curve of the taurine action to the right in parallel, indicating a competitive antagonism. A hyperpolarizing synaptic potential which was evoked by electrical stimulation of the upper region of the cerebellar molecular layer and recorded from a Purkinje cell dendrite, was reversed to a depolarizing one at a membrane potential of -70 mV. The hyperpolarization induced by exogenously applied taurine was also reversed at the same potential. Moreover, TAG (200 microM) completely and reversibly blocked the synaptic potential. These results suggest that taurine may be an inhibitory neurotransmitter in stellate neuronal synapses on Purkinje cell dendrites.