Effects of chlorpromazine and trinitrophenol on the membrane motor of outer hair cells.
The motile activity of outer hair cells' cell body is associated with large nonlinear capacitance due to a membrane motor that couples electric displacement with changes in the membrane area, analogous to piezoelectricity. This motor is based on prestin, a member of the SLC26 family of anion transporters and utilizes the electric energy available at the plasma membrane associated with the sensory function of these cells. To understand detailed mechanism of this motile activity, we examined the effect of amphipathic ions, cationic chlorpromazine and anionic trinitrophenol, which are thought to change the curvature of the membrane in opposite directions. We found that both chemicals reduced cell length at the holding potential of -75 mV and induced positive shifts in the cells' voltage dependence. The shift observed was approximately 10 mV for 500 microM trinitrophenol and 20 mV for 100 microM cationic chlorpromazine. Length reduction at the holding potential and voltage shifts of the motile activity were well correlated. The voltage shifts of nonlinear capacitance were not diminished by eliminating the cells' turgor pressure or by digesting the cortical cytoskeleton. These observations suggest that the membrane motor undergoes conformational transitions that involve changes not only in membrane area but also in bending stiffness.
Fang
Jie
J
Section on Biophysics, Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
Iwasa
K H
KH
D000465:Algorithms; D000818:Animals; D001692:Biological Transport; D001703:Biophysics / Q000379:methods*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology*; D003238:Connective Tissue; D018492:Dopamine Antagonists / Q000494:pharmacology; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000378:metabolism*; D007477:Ions; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D010851:Picrates / Q000494:pharmacology*; D014475:Uncoupling Agents / Q000494:pharmacology
D018492:Dopamine Antagonists; D007477:Ions; D010851:Picrates; D014475:Uncoupling Agents; C005858:picric acid; D002746:Chlorpromazine