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• Articles by Y.C. Wu
• Articles by R. Fettiplace

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• Tonotopic Variation in the Conductance of the Hair Cell Mech...

  Tonotopic Variation in the Conductance of the Hair Cell Mechanotransducer Channel Neuron, Volume 40, Issue 5, 4 December 2003, Pages 983-990 Anthony J Ricci, Andrew C Crawford and Robert Fettiplace Summary Hair cells in the vertebrate cochlea are arranged tonotopically with their characteristic frequency (CF), the sound frequency to which they are most sensitive, changing systematically with position. Single mechanotransducer channels of hair cells were characterized at different locations in the turtle cochlea. In 2.8 mM external Ca, the channel's chord conductance was 118 pS (range 80–163 pS), which nearly doubled (range 149–300 pS) on reducing Ca to 50 μM. In both Ca concentrations, the conductance was positively correlated with hair cell CF. Variation in channel conductance can largely explain the increases in size of the macroscopic transducer current and speed of adaptation with CF. It suggests diversity of transducer channel structure or environment along the cochlea that may be an important element of its tonotopic organization. Summary | Full Text | PDF (192 kb)

• Clues to the cochlear amplifier from the turtle ear

  Clues to the cochlear amplifier from the turtle ear Trends in Neurosciences, Volume 24, Issue 3, 1 March 2001, Pages 169-175 Robert Fettiplace, Anthony J Ricci and Carole M Hackney Abstract Sound stimuli are detected in the cochlea by vibration of hair bundles on sensory hair cells, which activates mechanotransducer ion channels and generates an electrical signal. Remarkably, the process can also work in reverse with additional force being produced by the ion channels as they open and close, evoking active movements of the hair bundle. These movements could supplement the energy of the sound stimuli but to be effective they would need to be very fast. New measurements in the turtle ear have shown that such active bundle movements occur with delays of less than a millisecond, and are triggered by the entry of Ca into the cell via the mechanotransducer channel. Furthermore, their speed depends on the frequency to which the hair cell is most sensitive, suggesting that such movements could be important in cochlear amplification and frequency discrimination. Abstract | Full Text | PDF (277 kb)

• Modeling Hair Cell Tuning by Expression Gradients of Potassi...

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Abstract

Hair cells in the turtle cochlea are frequency-tuned by a mechanism involving the combined activation of voltage-sensitive Ca2+ channels and Ca(2+)-activated K+ (KCa) channels. The main determinants of a hair cell's characteristic frequency (Fo) are the KCa channels' density and kinetics, both of which change systematically with location in the cochlea in conjunction with the observed frequency map. We have developed a model based on the differential expression of two KCa channel subunits, which when accompanied by concurrent changes in other properties (e.g., density of Ca2+ channels and inwardly rectifying K+ channels), will generate sharp tuning at frequencies from 40 to 600 Hz. The kinetic properties of the two subunits were derived from previous single-channel analysis, and it was assumed that the subunits (A and B) combine to form five species of tetrameric channel (A4, A3B, A2B2, AB3, and B4) with intermediate kinetics and overlapping distribution. Expression of KCa and other channels was assumed to be regulated by diffusional gradients in either one or two chemicals. The results are consistent with both current- and voltage-clamp data on turtle hair cells, and they show that five channel species are sufficient to produce smooth changes in both Fo and kinetics of the macroscopic KCa current. Other schemes for varying KCa channel kinetics are examined, including one that allows extension of the model to the chick cochlea to produce hair cells with Fo's from 130 to 4000 Hz. A necessary assumption in all models is a gradient in the values of the parameters identified with the cell's cytoplasmic Ca2+ buffer.