Mechanotransduction Currents Research Articles

The Transduction Channel Filter in Auditory Hair Cells

In the first step in auditory transduction, sound-induced vibrations of the stereociliary bundles on the sensory hair cells are converted into electrical signals by opening of mechanotransducer channels. Faithful transduction and hence auditory performance will be limited by the kinetic properties of these channels. We have measured the time course of mechanotransducer currents in turtle and rat auditory hair cells during rapid deflections of the hair bundle. Current activation in the turtle had a time constant that decreased 10-fold with stimulus amplitude to a limiting value of approximately 50 micros. Lowering the external Ca2+ concentration slowed both activation and adaptation time constants. Similar effects were seen in hair cells tuned to low and high frequencies, but the overall kinetics was slower in low-frequency cells. In rat outer hair cells, the time courses of both activation and adaptation were at least 10-fold faster. Although activation kinetics was too fast to characterize accurately, the adaptation time constants in the rat, like the turtle, were Ca2+ dependent and faster in hair cells tuned to higher frequencies. The results imply that mechanotransducer channels operate similarly in turtle and rat but are faster in the mammal to accommodate its higher frequency range of hearing. We suggest that the kinetics of channel activation and adaptation imposes a bandpass filter on transduction, with a center frequency matched to the frequencies detected by the hair cell, which may improve the signal-to-noise ratio near threshold.

Developmental Assembly of Transduction Apparatus in Chick Basilar Papilla

Hair cells, the sensory receptors of auditory and vestibular systems, use a transducer apparatus that renders them remarkably sensitive to mechanical displacement as minute as 1 nm. To study the embryonic development of the transducer apparatus in hair cells of the chick auditory papilla, we examined hair cells that have been labeled with N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) pyridiniumdibromide, which has been shown to permeate the transducer channels. In addition, mechanotransduction currents were recorded directly using whole-cell patch-clamp techniques. The structure of the hair bundle was examined using scanning electron microscopy, and immunofluorescence labeling for myosin 1c, myosin 7a, and plasma membrane Ca2+ ATPase 2 was studied to determine the developmental expression of these proteins in embryonic chick papillas. We demonstrate that the transducer apparatus is assembled jointly at embryonic day 11 (E11) of the developing chick basilar papilla. The resting open probability of the transducer channels was high at E12 (approximately 0.5) and remained substantially elevated at E14-16; it then declined to the mature value of approximately 0.15 at E21. The displacement sensitivity of the transduction apparatus, the gating force, increased from E12 to E21. Although the expression of different components of the transducer apparatus and the transduction current peaked at approximately E14-16, marked refinement occurred beyond E16. For example, myosin 1c appeared diffusely localized in hair bundles from E12 to E16, but subsequently consolidated into punctate pattern. The fine temporal and precise spatial assembly of the transducer apparatus likely contributes toward the exquisite sensitivity of the transduction ensemble.

Inhibition of mechanotransducer currents in crayfish sensory neuron by CGS 9343B, a calmodulin antagonist

The effects of CGS 9343B (zaldaride maleate), a calmodulin antagonist, on mechanosensitive channels were examined in crayfish slowly adapting sensory neurons using the two-electrode voltage clamp technique. In addition to its inhibition of voltage-gated Na + and K + currents, CGS 9343B (<30 μM) blocked reversibly the receptor current in a dose-dependent and voltage-dependent manner with a dissociation constant ( K d) of 26.8 μM. The time course of the block was 265 s. Within the extension range of 3–30%, the reduction in receptor current was stimulus-independent and the gating mechanisms were not affected. Extracellular Ca 2+ was not necessary for its blocking effects. No changes in passive muscle tension were observed in the presence of 20 μM CGS 9343B. These results suggest that CGS 9343B, as a calmodulin antagonist, can also block mechanosensitive channels, possibly by being incorporated into the lipid membrane and/or interacting with the channel protein.