Effects of Salicylate on Plasma Membrane Mechanics

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Abstract
High concentrations of the amphipathic drug salicylate (Sal) block outer hair cell (OHC) electromotility resulting in reversible hearing loss. We used optical tweezers to study the effects of Sal on the mechanics of the cell plasma membrane. Membrane tethers were formed from guinea pig OHCs and cultured human embryonic kidney (HEK) cells as controls. HEK cells are commonly used in functional expression studies of electromotility. Effective tether viscosity (ηeff), steady-state tethering force extrapolated to zero pulling rate Fss(0), and time constant for tether growth (τtg) were estimated from the measurements of the instantaneous tethering force at different tether pulling rates. Average values of ηeff, Fss(0), and τtg for the OHC lateral wall plasma membrane and control cell plasma membrane remained the same after Sal perfusion, which is consistent with the hypothesis that Sal-induced reversible hearing loss appears to be more the result of its competition with essential anions and less the result of a change in plasma membrane mechanics.