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Effects of Chlorpromazine on Mechanical Properties of the Outer Hair Cell Plasma Membrane

David R. Murdock ^*, Sergey A. Ermilov ^*, Alexander A. Spector , Aleksander S. Popel , William E. Brownell  and Bahman Anvari ^*

^* Department of Bioengineering, Rice University, Houston, Texas; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland; and Department of Otorhinolaryngology and Communicative Sciences, Baylor College of Medicine, Houston, Texas

Correspondence: Address reprint requests to Bahman Anvari, Rice University, Dept. of Bioengineering, PO Box 1892, MS 142, Houston, TX 77251-1892. Tel.: 713-348-5870; Fax: 713-348-5877; E-mail: anvari{at}rice.edu.

An optical tweezers system was used to characterize the effects of chlorpromazine (CPZ) on the mechanical properties of the mammalian outer hair cell (OHC) through the formation of plasma membrane tethers. Such tethers exhibited force relaxation when held at a constant length for several minutes. We used a second-order generalized Kelvin body to model tether-force behavior from which several mechanical parameters were then calculated including stiffness, viscosity-associated measures, and force relaxation time constants. The results of the analysis portray a two-part relaxation process characterized by significantly different rates of force decay, which we propose is due to the local reorganization of lipids within the tether and the flow of external lipid into the tether. We found that CPZ's effect was limited to the latter phenomenon since only the second phase of relaxation was significantly affected by the drug. This finding coupled with an observed large reduction in overall tether forces implies a common basis for the drug's effects, the plasma membrane-cytoskeleton interaction. The CPZ-induced changes in tether viscoelastic behavior suggest that alterations in the mechanical properties of the OHC lateral wall could play a role in the modulation of OHC electromotility by CPZ.

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