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J. Biol. Chem., Vol. 275, Issue 40, 31038-31050, October 6, 2000
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From the The M2 ion channel protein of
influenza A virus is essential for mediating protein-protein
dissociation during the virus uncoating process that occurs when the
virus is in the acidic environment of the lumen of the secondary
endosome. The difficulty of determining the ion selectivity of this
minimalistic ion channel is due in part to the fact that the channel
activity is so great that it causes local acidification in the
expressing cells and a consequent alteration of reversal voltage,
Vrev. We have confirmed the high proton selectivity of the
channel (1.5-2.0 × 106) in both oocytes and
mammalian cells by using four methods as follows: 1) comparison of
Vrev with proton equilibrium potential; 2) measurement of
pHin and Vrev while
Na+out was replaced; 3) measurements with
limiting external buffer concentration to limit proton currents
specifically; and 4) comparison of measurements of
M2-expressing cells with cells exposed to a protonophore.
Increased currents at low pHout are due to true activation
and not merely increased [H+]out because
increased pHout stops the outward current of acidified cells. Although the proton conductance is the biologically relevant conductance in an influenza virus-infected cell, experiments employing methods 1-3 show that the channel is also capable of conducting NH4+, probably
by a different mechanism from H+.
Permeation and Activation of the M2 Ion Channel
of Influenza A Virus*
,,
**, and
Department of Neurobiology and Physiology
and the ¶ Department of Biochemistry, Molecular Biology, and
Cell Biology, Howard Hughes Medical Institute, Northwestern
University, Evanston, Illinois 60208-3500 and
§ Institut für Biologische Informationsverarbeitung,
Forschungszentrum, 52425 Juelich, Germany
*
This work was supported by United States Public Health
Service Research Grants AI-20201 (to R. A. L) and AI-31882 (to
L. H. P) from the NIAID, National Institutes of Health and Deutsche Forschungsgemeinschaft Shwerpuncktprogramm "Molekulare
Sinnesphysiologie" (to S. M. F. and U. B. K.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of
Neurobiology and Physiology, Hogan Hall, 2153 North Campus Dr.,
Northwestern University, Evanston, IL 60208-3500. Tel.: 847-491-7915;
Fax: 847-491-5211; E-mail: larry-pinto@northwestern.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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