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The properties, functions, and pathophysiology of maxi-anion channels

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Abstract

The maxi-anion channels (MACs) with a unitary conductance of 200–500 pS are detected in virtually every part of the whole body and found in cells from mammals to amphibia. The channels are normally silent but can be activated by physiologically/pathophysiologically relevant stimuli, such as osmotic, salt, metabolic, oxidative, and mechanical stresses, receptor activation, serum, heat, and intracellular Ca2+ rise. In some MACs, protein dephosphorylation is associated with channel activation. Among MACs so far studied, around 60 % (designated here as Maxi-Cl) possess, in common, the following phenotypical biophysical properties: (1) unitary conductance of 300–400 pS, (2) a linear current–voltage relationship, (3) high anion-to-cation selectivity with PCl/Pcation of >8, and (4) inactivation at positive and negative potentials over a certain level (usually ±20 mV). The pore configuration of the Maxi-Cl is asymmetrical with extracellular and intracellular radii of ∼1.42 and ∼1.16 nm, respectively, and a medial constriction down to ∼0.55–0.75 nm. The classical function of MACs is control of membrane potential and fluid movement. Permeability to ATP and glutamate turns MACs to signaling channels in purinergic and glutamatergic signal transduction defining them as a perspective target for drug discovery. The molecular identification is an urgent task that would greatly promote the developments in this field. A possible relationship between these channels and some transporters is discussed.

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Acknowledgments

This work was supported by JSPS KAKENHI Grants (A) and (B) to YO as well as (C) to RZS and TO, by those for Scientific Research on Priority Areas to YO, by NIPS visiting scientist fellowships to RZS, PGM, and MRI, and by Grants-in-Aid from the Center for Science and Technology and Academy of Sciences of Uzbekistan to RZS and PGM.

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Correspondence to Ravshan Z. Sabirov or Yasunobu Okada.

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This article is published as part of the Special Issue on “Molecular physiology of anion channels: dual function proteins and new structural motifs.”

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Sabirov, R.Z., Merzlyak, P.G., Islam, M.R. et al. The properties, functions, and pathophysiology of maxi-anion channels. Pflugers Arch - Eur J Physiol 468, 405–420 (2016). https://doi.org/10.1007/s00424-015-1774-5

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