Taurine Suppresses Ca2+-Permeable Glutamate Receptors in Retinal Third-Order Neurons

Abstract

Purpose: : Taurine is highly concentrated in retinal neurons however its function in signal transmission is largely unknown. Immunoantibody labeling results show that taurine and taurine transporters are present in photoreceptors and Off-bipolar cells, suggesting that the third-order neurons might receive juxtaposed inputs of glutamate and taurine. This study explores the regulation of glutamate induced Ca²⁺

Methods: : The effect of taurine on glutamate-induced Ca²⁺ and currents were recorded in enzymatically dissociated third-order neurons, prepared from salamander retina. Whole-cell recordings were performed on amacrine and ganglion cells, using an EPC-10 amplifier and HEKA software. Fluo-4AM dye was used to analyse changes in intracellular Ca²⁺ levels and changes were monitored with IP Lab 4.0 software.

Results: : Taurine was found to effectively suppress glutamate-induced Ca²⁺ in a dose-dependent manner. The effect was selectively inhibited by both strychnine and picrotoxin but not GABA-receptor antagonists. Taurine regulation of glutamate was also sensitive to a CaMKII inhibitor. Taurine-sensitive receptors were inhibited by a rapid Ca²⁺ influx through glutamate receptors in the neuron

Conclusions: : Taurine suppresses Ca2+ permeability of all ionotropic glutamate receptors, and is more pronounced on kainate and NMDA receptors than on AMPA receptors. The difference of taurine regulation of AMPA receptors implicates the functional distinction between synaptic receptors and extrasynaptic receptors. Our results indicate that 2mM taurine produced effects were partially blocked by strychnine and picrotoxin, but not GABA receptor antagonists. This is consistent with the pharmacological of taurine described in the previous studies. However, taurine sensitivity to GABA receptors might be changed with different combinations of receptor subunit. The reciprocal inhibition between taurine and glutamate may contribute to the fine-tuning of glutamate signals in the neurons.

Keywords: taurine • calcium • excitatory neurotransmitters