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Pflugers Arch. 2010 Mar;459(4):593-605. doi: 10.1007/s00424-009-0760-1. Epub 2009 Nov 28.

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

Author information

1
Department of Neurobiology and Physiology, Northwestern University, Hogan Hall, 2205 Tech Drive, Evanston, IL 60208-3500, USA.

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.

PMID:
19946785
PMCID:
PMC3428792
DOI:
10.1007/s00424-009-0760-1
[Indexed for MEDLINE]
Free PMC Article

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