Effects of alcohol on the outer hair cell protein Prestin (775.2)

Abstract

Prestin, a transmembrane motor protein, is a member of the SLC26 family and is highly expressed in mammalian outer hair cells located in the cochlea. Outer hair cells, in response to changes in membrane potentials, adjust in length and rigidity. The production of these mechanical changes is thought to amplify the vibrations in the cochlea, increasing hearing sensitivity in mammals by 100‐fold. Since its identification in 2000, prestin has been found to be the motor protein in outer hair cells and is necessary for electromotility of the outer hair cell and for cochlear amplification.At this point, while the structure of prestin remains a mystery, previous experiments have indicated that prestin is sensitive to the levels of cholesterol in the cell membrane. Alcohols, which are also known modulators of lipid bilayer properties, could have the potential to have an impact on prestin function. It has been established that the link between the nonlinear capacitance of prestin and its electromotility is a surrogate measure of prestin function. Therefore, the effects of six alcohols ‐ ethanol, butanol, pentanol, hexanol, nonanol, and decanol, were each assessed at differing concentrations using patch‐clamp electrophysiology on HEK cells expressing prestin. The alcohols were chosen to have chain lengths smaller than 13, as alcohols with chain lengths above this cutoff have been shown to have limited biological activity and low solubility in cell buffers. All six of the alcohols tested showed either a depolarizing or polarizing effect.Grant Funding Source: Supported by NSF, RICE University