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P2X7R large pore is partially blocked by pore forming proteins antagonists in astrocytes

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Abstract

The ATP-gated P2X7R (P2X7R) is a channel, which is involved in events, such as inflammation, cell death, and pain. The most intriguing event concerning P2X7R functions is the phenomenon of pore dilation. Once P2X7R is activated, the permeability of the plasma membrane becomes higher, leading to the permeation of 1000 Da-weight solutes. The mechanisms involved in this process remain unclear. Nevertheless, this event is not exclusively through P2X7R, as other proteins may form large pores in the plasma membrane. Recent evidence concerning pore formation reveals putative P2X7R and other pores-associated protein complexes, revealing cross-interactive pharmacological and biophysical issues. In this work, we showed results that corroborated with cross-interactive aspects with P2X7R and pores in astrocytes. These cells expressed most of the pores, including P2X7R. We discovered that different pore types open with peculiar characteristics, as both anionic and cationic charged solutes permeate the plasma membrane, following P2X7R activation. Moreover, we showed that both synergic and additive relationships are found within P2X7, cationic, and anionic large pores. Therefore, our data suggest that other protein-related pores are assembled following the formation of P2X7R pore.

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Acknowledgments

This work was supported by The National Counsel of Technological and Scientific Development (CNPq), the Foundation for Research Support of the State of Rio de Janeiro (Faperj), and the Oswaldo Cruz Institute.

Authors’ contributions

Faria performed the experiments, analyzed and interpreted the data, prepared the figures and wrote the paper. Reis isolated and plated the astrocyte cells. Ferreira performed the real-time PCR experiments, and supported the make-up of the text manuscript. Cezar-de-Mello and Moraes performed real-time PCR experiments.

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Authors and Affiliations

  1. Laboratory of Toxoplasmosis, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil

    Robson X. Faria

  2. Laboratory of Neurochemistry, Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Ricardo A. M. Reis

  3. Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil

    Leonardo G. B. Ferreira

  4. Laboratory of Leprosy, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil

    Paula F. T. Cezar-de-Mello & Milton O. Moraes

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  1. Robson X. Faria
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Faria, R.X., Reis, R.A.M., Ferreira, L.G.B. et al. P2X7R large pore is partially blocked by pore forming proteins antagonists in astrocytes. J Bioenerg Biomembr 48, 309–324 (2016). https://doi.org/10.1007/s10863-016-9649-9

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