The influence of cholesterol on the motility of cochlear outer hair cells and the motor protein prestin

摘要

Conclusions: We provide evidence that cholesterol reduces electromotility in a dose-dependent matter. The data show that cholesterol modulates electromotility mainly by influencing the motor protein prestin, less by affecting the passive membrane properties. Objectives: Elevated serum cholesterol is linked to inner ear disorders and may influence hearing by altering membrane properties of outer hair cells (OHCs) and by affecting the motor protein prestin. In this study we wanted to determine whether cholesterol modulates the electromotility of OHCs and if this modulation results from effects on the membrane properties or on the motor protein prestin. Materials and methods: The motile responses of 12 isolated OHCs were investigated at increasing concentrations of 0, 0.1, and 1 mM extracellular cholesterol using the patch clamp technique and continuous video image analysis. To study effects on prestin, experiments were performed in 12 cells with half activated protein function and concentrations of 0 and 1 mM cholesterol. Results: Cholesterol at a concentration of 0.1 mM had no effect on motility. A concentration of 1 mM reduced maximal evoked shortening significantly by 29% in the depolarizing and by 9% in the hyperpolarizing direction. Investigating half activated motor proteins, 1 mM cholesterol reduced movements significantly by 18%, elongations decreased nonsignificantly by 5%.