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ATP Signaling in Brain: Release, Excitotoxicity and Potential Therapeutic Targets

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Abstract

Adenosine 5′-triphosphate (ATP) is released as a genuine co-transmitter, or as a principal purinergic neurotransmitter, in an exocytotic and non-exocytotic manner. It activates ionotropic (P2X) and metabotropic (P2Y) receptors which mediate a plethora of functions in the brain. In particular, P2X7 receptor (P2X7R) are expressed in all brain cells and its activation can form a large pore allowing the passage of organic cations, the leakage of metabolites of up to 900 Da and the release of ATP itself. In turn, pannexins (Panx) are a family of proteins forming hemichannels that can release ATP. In this review, we summarize the progress in the understanding of the mechanisms of ATP release both in physiological and pathophysiological stages. We also provide data suggesting that P2X7R and pannexin 1 (Panx1) may form a large pore in cortical neurons as assessed by electrophysiology. Finally, the participation of calcium homeostasis modulator 1 is also suggested, another non-selective ion channel that can release ATP, and that could play a role in ischemic events, together with P2X7 and Panx1 during excitotoxicity by ATP.

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Acknowledgments

Work in our laboratory is supported by CIBERNED, Gobierno Vasco, MINECO, Eranet-Neuron and Universidad del País Vasco. A. C-M is a recipient of a postdoctoral position from CONACYT (México).

Conflict of interest

The authors declare that there is no conflict of interest.

Ethical Standards

The experiments of this work were conducted under the approval of our internal animal ethics committee (University of the Basque Country, UPV/EHU). Animals were handled in accordance with the European Communities Council Directive. All possible efforts were made to minimize animal suffering and the number of animals used.

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Authors and Affiliations

  1. Achucarro Basque Center for Neuroscience, Departamento de Neurociencias and CIBERNED, Universidad Del País Vasco, Leioa, Vizcaya, Spain

    Abraham Cisneros-Mejorado, Alberto Pérez-Samartín, Miroslav Gottlieb & Carlos Matute

  2. Neurotek-UPV/EHU, Parque Tecnológico de Bizkaia, Zamudio, Spain

    Alberto Pérez-Samartín & Carlos Matute

  3. Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovak Republic

    Miroslav Gottlieb

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  1. Abraham Cisneros-Mejorado
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  2. Alberto Pérez-Samartín
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  3. Miroslav Gottlieb
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  4. Carlos Matute
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Correspondence to Carlos Matute.

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Cisneros-Mejorado, A., Pérez-Samartín, A., Gottlieb, M. et al. ATP Signaling in Brain: Release, Excitotoxicity and Potential Therapeutic Targets. Cell Mol Neurobiol 35, 1–6 (2015). https://doi.org/10.1007/s10571-014-0092-3

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  • DOI: https://doi.org/10.1007/s10571-014-0092-3

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