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Intracellular accumulation of amino acids increases synaptic potentials in rat hippocampal slices

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Abstract

The application of high concentrations of taurine induces long-lasting potentiation of synaptic responses and axon excitability. This phenomenon seems to require the contribution of a transport system with a low affinity for taurine. The prototypic taurine transporter TauT (SLC6A6) was discarded by experimental evidence obtained in TauT-KO mice. The purpose of the present study was to determine whether the proton-coupled amino acid transporter 1 (PAT1; SLC36A1) which is a transport system with low affinity and high capacity for a great variety of amino acids including taurine, contributes to the taurine-induced synaptic potentiation. In rat hippocampal slices, the application of several amino acids (l- and d-alanine, l-glutamine, β-guanidinopropionic acid, glycine, l-histidine, l- and d-serine, sarcosine, l- and d-threonine) imitated the synaptic potentiation induced by taurine. The magnitude of the potentiation caused by some of these amino acids was even greater than that induced by taurine. By contrast, the application of other amino acids (l-arginine, betaine, l-leucine, l-methionine, l- and d-proline, and l-valine) did not induce potentiation. The behaviour of these different amino acids on synaptic potentiation is not compatible with a role of PAT1 in synaptic potentiation. There was a positive correlation between the accumulation of the different amino acids in the slice and the magnitude of synaptic potentiation induced by them. Some of the amino acids inducing synaptic potentiation, like taurine and l-threonine, also increased electrical resistance of the slice, whereas l-leucine did not modify this parameter. Modifications induced by either taurine or l-threonine in synaptic potentiation, slice resistance and amino acid accumulation were dependent on extracellular chloride concentration. These findings support the idea that the accumulation of amino acids throughout the action of transporters causes cell swelling enhancing the electrical resistance of the slice, which by itself could be sufficient to increase field synaptic potentials.

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Acknowledgements

This work was supported by a grant from “Instituto de Salud Carlos III” (PIU081067) to JMS. We thank Amparo Latorre, María José Asensio and José Barbado for technical assistance.

Funding

This work was supported by a grant from “Instituto de Salud Carlos III” (PIU081067) to J.M. Solís.

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Authors and Affiliations

  1. Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. de Colmenar Km 9.1, 28034, Madrid, Spain

    Javier G. Luengo, Iris Álvarez-Merz, Antonio S. Herranz, Rafael Martín del Río & José M. Solís

  2. Department of Pharmacology and Therapeutic, School of Medicine, Universidad Autónoma de Madrid, IRYCIS, Avda. Arzobispo Morcillo 4, 28029, Madrid, Spain

    Javier G. Luengo, Iris Álvarez-Merz & Jesús M. Hernández-Guijo

  3. Unidad de Neurología Experimental, Hospital Universitario Ramón y Cajal, IRYCIS, 28034, Madrid, Spain

    María-Dolores Muñoz

  4. Department of Neurobiology, McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    José C. González

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  1. Javier G. Luengo
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  2. María-Dolores Muñoz
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Correspondence to José M. Solís.

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The care and use of animals was carried out following the European Communities Council Directive (86/609/ECC). Protocols were approved by “Comité Ético de Bienestar Animal” at Hospital Universitario Ramón y Cajal (animal facilities ES280790000092).

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Luengo, J.G., Muñoz, MD., Álvarez-Merz, I. et al. Intracellular accumulation of amino acids increases synaptic potentials in rat hippocampal slices. Amino Acids 51, 1337–1351 (2019). https://doi.org/10.1007/s00726-019-02771-w

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