Permeation and activation of the M2 ion channel of influenza A virus

Jorgen A. Mould, Jason E. Drury, Stephan M. Fring, U. Benjamin Kaupp, Andrew Pekosz, Robert A. Lamb, Lawrence H. Pinto

Research output: Contribution to journalArticlepeer-review


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, V(rev). We have confirmed the high proton selectivity of the channel (1.5-2.0 x 106) in both oocytes and mammalian cells by using four methods as follows: 1) Comparison of V(rev) with proton equilibrium potential; 2) measurement of pH(in) and V(rev) while Na+(out) was replaced; 3) measuremerits 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 pH(out) are due to true activation and not merely increased [H+](out) because increased PH(out) 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 NH+/4, probably by a different mechanism from H+.

Original languageEnglish (US)
Pages (from-to)31038-31050
Number of pages13
JournalJournal of Biological Chemistry
Issue number40
StatePublished - Oct 6 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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