Na+ Modulates Anion Permeation and Block of P2X7 Receptors from Mouse Parotid Glands

Na+ Modulates Anion Permeation and Block of P2X7 Receptors from Mouse Parotid Glands We previously reported that mouse parotid acinar cells display anion conductance (I ATPCl) when stimulated by external ATP in Na+-free extracellular solutions. It has been suggested that the P2X7 receptor channel (P2X7R) might underlie I ATPCl. In this work we show that I ATPCl can be activated by ATP, ADP, AMP-PNP, ATPγS and CTP. This is consistent with the nucleotide sensitivity of P2X7R. Accordingly, acinar cells isolated from P2X 7 R −/− mice lacked I ATPCl. Experiments with P2X7R heterologously expressed resulted in ATP-activated currents (I ATP-P2X7) partially carried by anions. In Na+-free solutions, I ATP-P2X7 had an apparent anion permeability sequence of SCN− > I− ≅ NO 3 − > Br− > Cl− > acetate, comparable to that reported for I ATPCl under the same conditions. However, in the presence of physiologically relevant concentrations of external Na+, the Cl− permeability of I ATP-P2X7 was negligible, although permeation of Br− or SCN− was clearly resolved. Relative anion permeabilities were not modified by addition of 1 mm carbenoxolone, a blocker of Pannexin-1. Moreover, cibacron blue 3GA, which blocks the Na+ current activated by ATP in acinar cells but not I ATPCl, blocked I ATP-P2X7 in a dose-dependent manner when Na+ was present but failed to do so in tetraethylammonium containing solutions. Thus, our data indicate that P2X7R is fundamental for I ATPCl generation in acinar cells and that external Na+ modulates ion permeability and conductivity, as well as drug affinity, in P2X7R. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals
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Publisher
Springer-Verlag
Copyright
Copyright © 2008 by Springer Science+Business Media, LLC
Subject
Life Sciences; Human Physiology ; Biochemistry, general
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-008-9115-7
Publisher site
See Article on Publisher Site

Abstract

We previously reported that mouse parotid acinar cells display anion conductance (I ATPCl) when stimulated by external ATP in Na+-free extracellular solutions. It has been suggested that the P2X7 receptor channel (P2X7R) might underlie I ATPCl. In this work we show that I ATPCl can be activated by ATP, ADP, AMP-PNP, ATPγS and CTP. This is consistent with the nucleotide sensitivity of P2X7R. Accordingly, acinar cells isolated from P2X 7 R −/− mice lacked I ATPCl. Experiments with P2X7R heterologously expressed resulted in ATP-activated currents (I ATP-P2X7) partially carried by anions. In Na+-free solutions, I ATP-P2X7 had an apparent anion permeability sequence of SCN− > I− ≅ NO 3 − > Br− > Cl− > acetate, comparable to that reported for I ATPCl under the same conditions. However, in the presence of physiologically relevant concentrations of external Na+, the Cl− permeability of I ATP-P2X7 was negligible, although permeation of Br− or SCN− was clearly resolved. Relative anion permeabilities were not modified by addition of 1 mm carbenoxolone, a blocker of Pannexin-1. Moreover, cibacron blue 3GA, which blocks the Na+ current activated by ATP in acinar cells but not I ATPCl, blocked I ATP-P2X7 in a dose-dependent manner when Na+ was present but failed to do so in tetraethylammonium containing solutions. Thus, our data indicate that P2X7R is fundamental for I ATPCl generation in acinar cells and that external Na+ modulates ion permeability and conductivity, as well as drug affinity, in P2X7R.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Jul 1, 2008

References

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