Merck

Membrane cholesterol modulates cochlear electromechanics.

Pflugers Archiv : European journal of physiology (2011-03-05)
William E Brownell, Stefan Jacob, Pierre Hakizimana, Mats Ulfendahl, Anders Fridberger
ABSTRACT

Changing the concentration of cholesterol in the plasma membrane of isolated outer hair cells modulates electromotility and prestin-associated charge movement, suggesting that a similar manipulation would alter cochlear mechanics. We examined cochlear function before and after depletion of membrane cholesterol with methyl-β-cyclodextrin (MβCD) in an excised guinea pig temporal bone preparation. The mechanical response of the cochlear partition to acoustic and/or electrical stimulation was monitored using laser interferometry and time-resolved confocal microscopy. The electromechanical response in untreated preparations was asymmetric with greater displacements in response to positive currents. Exposure to MβCD increased the magnitude and asymmetry of the response, without changing the frequency tuning of sound-evoked mechanical responses or cochlear microphonic potentials. Sodium salicylate reversibly blocked the enhanced electromechanical response in cholesterol depleted preparations. The increase of sound-evoked vibrations during positive current injection was enhanced following MβCD in some preparations. Imaging was used to assess cellular integrity which remained unchanged after several hours of exposure to MβCD in several preparations. The enhanced electromechanical response reflects an increase in outer hair cell electromotility and may reveal features of cholesterol distribution and trafficking in outer hair cells.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Earle′s Balanced Salts, With sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Earle′s Balanced Salts, With sodium bicarbonate, without phenol red, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Earle′s Balanced Salts, With sodium bicarbonate, without calcium chloride and magnesium sulfate, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Methyl-β-cyclodextrin, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Methyl-β-cyclodextrin, average Mn 1310
Sigma-Aldrich
Methyl-β-cyclodextrin
Sigma-Aldrich
Methyl-β-cyclodextrin, produced by Wacker Chemie AG, Burghausen, Germany, ≥95.0% cyclodextrin basis (calculated)
Sigma-Aldrich
Methyl-β-cyclodextrin, Produced by Wacker Chemie AG, Burghausen, Germany, Life Science, ≥98.0% cyclodextrin basis