Selective proton permeability and pH regulation of the influenza virus M2 channel expressed in mouse erythroleukaemia cells

I. V. Chizhmakov, F. M. Geraghty, D. C. Ogden, A. Hayhurst, M. Antoniou, A. J. Hay

Research output: Contribution to journalArticle

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Abstract

1. The M2 protein of influenza A virus is implicated in transmembrane pH regulation during infection. Whole-cell patch clamp of mouse erythroleukaemia cells expressing the M2 protein in the surface membrane showed a conductance due to M2 which was specifically blocked by the anti-influenza drug rimantadine. 2. The ion selectivity of the rimantadine-sensitive current through M2 was determined. Reversal potentials were close to equilibrium potentials for transmembrane pH gradients and not to those for Na+, K+ or Cl- concentration gradients. M2 permeability to Na+ relative to H+ was estimated to be less than 6 x 10-7. 3. The M2 conductance increased as external pH decreased below 8.5 and approached saturation at an external pH of 4, effects attributable to increased permeability due to increased driving potential and to activation by low external pH. Both activation and permeation could be described by interaction of protons with sites on M2, with apparent dissociation constants of approximately 0.1 μM and 1 μM, respectively, under physiological conditions. 4. The M2 protein can transfer protons selectively across membranes with the H+ electrochemical gradient, properties consistent with its role in modifying virion and trans-Golgi pH during virus infection.

Original languageEnglish (US)
Pages (from-to)329-336
Number of pages8
JournalJournal of Physiology
Volume494
Issue number2
StatePublished - Jul 15 1996
Externally publishedYes

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Leukemia, Erythroblastic, Acute
Orthomyxoviridae
Protons
Permeability
Rimantadine
Proton-Motive Force
Membranes
Virus Diseases
Virion
Membrane Potentials
Human Influenza
Membrane Proteins
Ions
Infection
Pharmaceutical Preparations
Proteins

ASJC Scopus subject areas

  • Physiology

Cite this

Chizhmakov, I. V., Geraghty, F. M., Ogden, D. C., Hayhurst, A., Antoniou, M., & Hay, A. J. (1996). Selective proton permeability and pH regulation of the influenza virus M2 channel expressed in mouse erythroleukaemia cells. Journal of Physiology, 494(2), 329-336.

Selective proton permeability and pH regulation of the influenza virus M2 channel expressed in mouse erythroleukaemia cells. / Chizhmakov, I. V.; Geraghty, F. M.; Ogden, D. C.; Hayhurst, A.; Antoniou, M.; Hay, A. J.

In: Journal of Physiology, Vol. 494, No. 2, 15.07.1996, p. 329-336.

Research output: Contribution to journalArticle

Chizhmakov, IV, Geraghty, FM, Ogden, DC, Hayhurst, A, Antoniou, M & Hay, AJ 1996, 'Selective proton permeability and pH regulation of the influenza virus M2 channel expressed in mouse erythroleukaemia cells', Journal of Physiology, vol. 494, no. 2, pp. 329-336.
Chizhmakov IV, Geraghty FM, Ogden DC, Hayhurst A, Antoniou M, Hay AJ. Selective proton permeability and pH regulation of the influenza virus M2 channel expressed in mouse erythroleukaemia cells. Journal of Physiology. 1996 Jul 15;494(2):329-336.
Chizhmakov, I. V. ; Geraghty, F. M. ; Ogden, D. C. ; Hayhurst, A. ; Antoniou, M. ; Hay, A. J. / Selective proton permeability and pH regulation of the influenza virus M2 channel expressed in mouse erythroleukaemia cells. In: Journal of Physiology. 1996 ; Vol. 494, No. 2. pp. 329-336.
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