A-M2 proton channel of the influenza A virus is a target for the anti-flu drugs amantadine and rimantadine. However, a rapid increase of the virus resistance to these drugs was recorded in the past decade. Therefore, new needs for the development of effective, M2-targeted drugs have emerged. This application note describes the use of SURFE²R™ Technology platform with a 96-biosensor array for the time-resolved, electrical measurement of the A-M2 channel activity. A-M2 was activated by pH jumps through a rapid exchange of the "non-activating" solution of pH 7 by the "activating" solution of pH 6. Electrical currents detected with the wild-type A-M2 were inhibited by amantadine. In contrary, the activity of the amantadine-resistant S31N mutant was not inhibited at the corresponding amantadine concentrations. The assay was highly sensitive with an amantadine IC₅₀ of 0.3 μM for the wild-type A-M2. As expected, both, the wild-type A-M2 and the S31N mutant activities were inhibited by copper. The data demonstrate the feasibility of the technology for high-content functional and pharmacological studies of the A-M2 activity in a 96-array format.