Solid-supported membrane technology for the investigation of the influenza A virus M2 channel activity

Victoria Balannik, Petr Obrdlik, Samsoon Inayat, Catrin Steensen, Jun Wang, Joshua M. Rausch, William F. Degrado, Bela Kelety, Lawrence H. Pinto

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Influenza A virus encodes an integral membrane protein, A/M2, that forms a pH-gated proton channel that is essential for viral replication. The A/M2 channel is a target for the anti-influenza drug amantadine, although the effectiveness of this drug has been diminished by the appearance of naturally occurring point mutations in the channel pore. Thus, there is a great need to discover novel anti-influenza therapeutics, and, since the A/M2 channel is a proven target, approaches are needed to screen for new classes of inhibitors for the A/M2 channel. Prior in-depth studies of the activity and drug sensitivity of A/M2 channels have employed labor-intensive electrophysiology techniques. In this study, we tested the validity of electrophysiological measurements with solid-supported membranes (SSM) as a less labor-intensive alternative technique for the investigation of A/M2 ion channel properties and for drug screening. By comparing the SSM-based measurements of the activity and drug sensitivity of A/M2 wild-type and mutant channels with measurements made with conventional electrophysiology methods, we show that SSM-based electrophysiology is an efficient and reliable tool for functional studies of the A/M2 channel protein and for screening compounds for inhibitory activity against the channel.

Original languageEnglish (US)
Pages (from-to)593-605
Number of pages13
JournalPflugers Archiv European Journal of Physiology
Volume459
Issue number4
DOIs
StatePublished - Mar 2010
Externally publishedYes

Keywords

  • A/M2 channel
  • Influenza a virus
  • Proton channel
  • SSM-based electrophysiology
  • SURFER
  • Technology

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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