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Biophysical Journal 69: 1363-1371 (1995)
© 1995 the Biophysical Society
Howard Hughes Medical Institute, Northwestern University, Evanston, Illinois 60208-3500, USA.
ABSTRACT
To test the hypothesis that transmembrane domain histidine residue 37 of the M2 ion channel of influenza A virus mediates the low pH-induced activation of the channel, the residue was changed to glycine, glutamate, arginine, or lysine. The wild-type and altered M2 proteins were expressed in oocytes of Xenopus laevis and membrane currents were recorded. The mass of protein expressed in individual oocytes was measured using quantitative immunoblotting and correlated with membrane currents. Oocytes expressing the M2-H37G protein had a voltage-independent conductance with current-voltage relationship similar to that of the wild-type M2 channel. The conductance of the M2-H37G protein was reversibly inhibited by the M2 ion channel blocker amantadine and was only very slightly modulated by changes in pHout over the range pH 5.4 to pH 8.2. Oocytes expressing the M2-H37E protein also had a voltage-independent conductance with a current-voltage relationship similar to that of the wild-type M2 channel. The conductance of the M2-H37E protein was reversibly inhibited by amantadine and was also only very slightly modulated by changes in pHout over the range pH 5.4 to pH 8.2. These slight alterations in conductance of the mutant ion channels on changes in pHout are in striking contrast to the 50-fold change in conductance seen for the wild-type M2 channel over the range pH 4.5 to pH 8.2. The specific activity of the M2-H37G protein was 1.36 +/- 0.37 microA/ng and the specific activity of the M2-H37E protein was 30 +/- 3 microA/ng at pH 6.2.(ABSTRACT TRUNCATED AT 250 WORDS)
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