Ion channel activity of influenza A virus M₂ protein: Characterization of the amantadine block

The influenza A virus M₂ integral membrane protein has ion channel activity which can be blocked by the antiviral drug amantadine. The M₂ protein transmembrane domain is highly conserved in amino acid sequence for all the human, swine, equine, and avian strains of influenza A virus, and thus, known amino acid differences could lead to altered properties of the M₂ ion channel. We have expressed in oocytes of Xenopus laevis the M₂ protein of human influenza virus A/Udorn/72 and the avian virus A/chicken/Germany/34 (fowl plague virus, Rostock) and derivatives of the Rostock ion channel altered in the presumed pore region. The pH of activation of the M₂ ion channels and amantadine block of the M₂ ion channels were investigated. The channels were found to be activated by pH in a similar manner but differed in their apparent K_is for amantadine block.